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Results for “Functional potential”

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PubMed2026

Clinical, genetic and bioinformatic analysis of Saudi families with Joubert syndrome and related disorders.

BACKGROUND: Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies caused by pathogenic variants in over 40 genes, mainly encoding ciliary proteins. However, data on JSRD in the Saudi population remain limited. This study aimed to identify novel and reported JSRD-causing variants in Saudi families and analyze their potential functional impact on protein structure using advanced computational tools. METHODS: Patients with genetically or clinically confirmed/suspected JSRD were recruited according to ethical protocols. Clinical data were collected, and exome sequencing was performed, followed by Sanger validation of identified variant. Pathogenicity was assessed using bioinformatics tools, while conservation, expression and RNA structure analyses were conducted to evaluate the potential functional consequences. RESULTS: Homozygous variants were identified in three consanguineous Saudi families, including a novel stop-gain variant in KIF7 (c.2992 C > T; p.(Gln998Ter)), and novel splice-site variant in CEP104 (c.489 + 1G > A) and a previously reported splice-site variant in TMEM237 (c.869 + 1G > A). All variants were predicted to be pathogenic as per ACMG criteria and located in highly conserved regions, suggesting potential functional impact. RNA analysis suggested possible alterations in folding. CONCLUSION: This study identified three pathogenic variants in JSRD-related genes in Saudi families, including two novel variants. These findings expand the variant spectrum for JSRD, particularly in the Saudi population. Establishing a comprehensive regional variant database is essential for improving molecular diagnosis and genetic counseling in population with high consanguinity. Finally, these results highlight the need for further functional studies to validate their pathogenicity and elucidate their role in JSRD pathogenesis.

Humans↗

PubMed1997

Viscoelastic relaxation and regional blood flow response to spinal cord compression and decompression.

STUDY DESIGN: To better understand the relationships between primary mechanical factors of spinal cord trauma and secondary mechanisms of injury, this study evaluated regional blood flow and somatosensory evoked potential function in an in vivo canine model with controlled velocity spinal cord displacement and real-time piston-spinal cord interface pressure feedback. OBJECTIVES: To determine the effect of regional spinal cord blood flow and viscoelastic cord relaxation on recovery of neural conduction, with and without spinal cord decompression. SUMMARY OF BACKGROUND DATA: The relative contribution of mechanical and vascular factors on spinal cord injury remains undefined. METHODS: Twelve beagles were anesthetized and underwent T13 laminectomy. A constant velocity spinal cord compression was applied using a hydraulic loading piston with a subminiature pressure transducer rigidly attached to the spinal column. Spinal cord displacement was stopped when somatosensory evoked potential amplitudes decreased by 50% (maximum compression). Six animals were decompressed 5 minutes after maximum compression and were compared with six animals who had spinal cord displacement maintained for 3 hours and were not decompressed. Regional spinal cord blood flow was measured with a fluorescent microsphere technique. RESULTS: At maximum compression, regional spinal cord blood flow at the injury site fell from 19.0 +/- 1.3 mL/100 g/min to 12.6 +/- 1.0 mL/100 g/min, whereas piston-spinal cord interface pressure was 30.5 +/- 1.8 kPa, and cord displacement measured 2.1 +/- 0.1 mm (mean +/- SE). Five minutes after the piston translation was stopped, the spinal cord interface pressure had dissipated 51%, whereas the somatosensory evoked potential amplitudes continued to decrease to 16% of baseline. In the sustained compression group, cord interface pressure relaxed to 13% of maximum within 90 minutes; however, no recovery of somatosensory evoked potential function occurred, and regional spinal cord blood flow remained significantly lower than baseline at 30 and 180 minutes after maximum compression. In the six animals that underwent spinal cord decompression, somatosensory evoked potential function and regional spinal cord blood flow recovered to baseline 30 minutes after maximum compression. CONCLUSIONS: Despite rapid cord relaxation of more than 50% within 5 minutes after maximum compression, somatosensory evoked potential conduction recovered only with early decompression. Spinal cord decompression was associated with an early recovery of regional spinal cord blood flow and somatosensory evoked potential recovery. By 3 hours, spinal cord blood flow was similar in both the compressed and decompressed groups, despite that somatosensory evoked potential recovery occurred only in the decompressed group.

Animals↗

PubMed2001

Metal-metal and carbon-carbon bonds as potential components of molecular batteries.

The reductive coupling of [M(salophen)] derivatives, where M is an early transition metal and salophen is N,N'-o-phenylenebis(salicylideneaminato) dianion, led to the formation of dimers linked through C-C and M-M bonds. Both of these bonds can potentially function as electron reservoirs: each bond can be used as a reversible source of a pair of electrons under the condition that it is not chemically transformed by the incoming substrate which functions as an electron acceptor. To explore this potential function as well as the competition in the redox processes between C-C and M-M bonds within the same molecular framework, we investigated the reduction of [(tBu4-salophen)NbCl3] (1) and [(tBu4-salophen)MoCl2] (7) as model compounds. In the former case, the reduction led to [(Nb-Nb)(tBu4-*salophen2*)] (2) which contains both a Nb-Nb bond (2.6528(7) A) and two C-C bonds across two imino groups of the ligand. Complex 2 can be reduced further to a transient compound 5 that contains an Nb=Nb bond. In the second case, the reduction of 7 by two electrons led to [(Mo[triplebond]Mo)(tBu4-salophen)2] (8), which does not contain any C-C linkages between the two salophen units. Complexes 2 and 5 are able to transfer one pair and two pairs of electrons, respectively, to give compounds 3, 4, and 6, with the consequent cleavage of the Nb-Nb and Nb=Nb bonds. In the present case, it is surprising that the C-C bonds do not participate in the reduction of the substrates. A careful theoretical treatment anticipates, both in the case of 1 and 7, the preferential formation of metal-metal bonds upon reduction. This is indeed the case for 7, but not for 1, where the formation of C-C bonds competes with that of M-M bonds, the latter being the first ones, however, to be involved in electron-transfer reactions. The theoretical approach allowed us to investigate the possibility of intramolecular electron transfer from C-C bonds to M-M bonds and vice versa.

Journal Article↗

PubMed1992

Self-organizing maps: ordering, convergence properties and energy functions.

We investigate the convergence properties of the self-organizing feature map algorithm for a simple, but very instructive case: the formation of a topographic representation of the unit interval [0, 1] by a linear chain of neurons. We extend the proofs of convergence of Kohonen and of Cottrell and Fort to hold in any case where the neighborhood function, which is used to scale the change in the weight values at each neuron, is a monotonically decreasing function of distance from the winner neuron. We prove that the learning dynamics cannot be described by a gradient descent on a single energy function, but may be described using a set of potential functions, one for each neuron, which are independently minimized following a stochastic gradient descent. We derive the correct potential functions for the one- and multi-dimensional case, and show that the energy functions given by Tolat (1990) are an approximation which is no longer valid in the case of highly disordered maps or steep neighborhood functions.

Algorithms↗

PubMed2001

Novel cross-linked homogeneous polyacrylamide gels with improved separation properties: investigation of the cross-linker functionality.

Polyacrylamide (PAAm) gels were synthesized using cross-linkers with their potential functionality (twice the number of double bonds of a cross-linker) varying from six to sixteen. Improved electrophoretic separation and highly desirable porosity and sieving properties were observed for most of the PAAm gels containing novel cross-linkers. An increase in the potential functionality of cross-linkers used in PAAm gels was an important factor, influencing the pore size and pore size distribution of the network.

Electrophoresis, Polyacrylamide Gel↗

PubMed2006

The role of the Niemann-Pick C1-like 1 protein in the subcellular transport of multiple lipids and their homeostasis.

PURPOSE OF REVIEW: In the past 2 years the Niemann-Pick C1-like 1 protein has rapidly emerged as a key regulator of intestinal cholesterol absorption. This review covers the limited number of published reports to develop a hypothesis of the potential function of Niemann-Pick C1-like 1 protein and outlines questions that should be addressed in future studies. RECENT FINDINGS: Considerable disagreement regarding the potential function and subcellular location of Niemann-Pick C1-like 1 protein has complicated interpretation of published results and evaluation of their biologic significance. Recent reports suggest, however, that Niemann-Pick C1-like 1 protein plays a key role in modulating the subcellular fate of multiple lipids including cholesterol and sphingolipids. In addition, this function may require Niemann-Pick C1-like 1 protein to move between different cellular locations. SUMMARY: This paper proposes a model of Niemann-Pick C1-like 1 protein function based on available data and on knowledge of its close relative and homologue the Niemann-Pick C1 protein, whose precise function, albeit still elusive, is more extensively characterized. It also raises new questions with respect to Niemann-Pick C1-like 1 protein function and discusses potential future directions.

Animals↗

PubMed1990

Compound action potential input/output functions in young and quiet-aged gerbils.

Auditory-nerve compound action potentials (CAP) and cochlear microphonic (CM) potentials were measured with round window electrodes in two sets of quiet-reared gerbils: young (N = 9 ears, 4-7 months) and aged (N = 11 ears, 35-37 months). CAP thresholds, measured at probe frequencies from 0.5 to 25.6 kHz, are plotted as audibility curves. Input/output (I/O) functions were derived from CAP and CM amplitude measurements at six frequencies. When compared to young controls, CAP audibility curves from aged animals all show some degree of threshold shift, ranging from minimal to severe, as well as increased variability. Our data suggest that some of the variability in the aged-animal audibility curves can be attributed to variations in individual genetic factors. Maximum CAP amplitudes for the aged animals average significantly less than those of the young controls at all frequencies tested. Young control I/O functions are generally steeper than those of the aged gerbils. Differences in the CM amplitudes of the young and aged gerbils are not as clear cut as the differences in the CAP. Possible mechanisms explaining the decrease in amplitudes and slopes of the CAP I/O functions in aged animals include changes in numbers or thresholds of primary ganglion cells, or a decrease in synchrony in discharges of auditory-nerve fibers.

Action Potentials↗

PubMed2001

Ethanol potentiates the function of the human dopamine transporter expressed in Xenopus oocytes.

Ethanol alters a variety of properties of brain dopaminergic neurons including firing rate, synthesis, release, and metabolism. Recent studies suggest that ethanol's action on central dopamine systems may also involve modulation of dopamine transporter (DAT) activity. The human DAT was expressed in Xenopus oocytes to examine directly the effects of ethanol on transporter function. [3H]Dopamine (100 nM) accumulation into DAT-expressing oocytes increased significantly in response to ethanol (10 min; 10-100 mM). In two-electrode voltage-clamp experiments, DAT-mediated currents were also enhanced significantly by ethanol (10-100 mM). The magnitude of the ethanol-induced potentiation of DAT function depended on ethanol exposure time and substrate concentration. Cell surface DAT binding ([3H]WIN 35,428; 4 nM) also increased as a function of ethanol exposure time. Thus, the increase in dopamine uptake was associated with a parallel increase in the number of DAT molecules expressed at the cell surface. These experiments demonstrate that DAT-mediated substrate translocation and substrate-associated ionic conductances are sensitive to intoxicating concentrations of ethanol and suggest that DAT may represent an important site of action for ethanol's effects on central dopaminergic transmission. A potential mechanism by which ethanol acts to enhance DAT function may involve regulation of DAT expression on the cell surface.

Animals↗

PubMed1982

Antithrombotic effects of drugs which suppress platelet function: their potential in prevention growth of tumour cells.

Four drugs that inhibit platelet function have been evaluated for their antithrombotic effects in humans. These are aspirin, dipyridamole, hydroxychloroquine and sulphinpyrazone. Aspirin has been shown to reduce the number of transient ischemic attacks (TIA), stroke and death in patients with multiple TIA. The reduction in TIA was greatest in males who were normotensive and when there was an angiographically demonstrated lesion in the carotid artery that accounted for the symptoms. Aspirin reduced venous thrombosis and non-fatal and fatal pulmonary embolism in patients after surgery for fractured hip and after elective hip replacement. There is evidence that the prophylactic effect of aspirin may be greater in male patients. Aspirin reduced the frequency of arteriovenous shunt thrombosis. Aspirin abolished symptoms in patients with peripheral ischemia associated with thrombocytosis and spontaneous platelet aggregation. There is no conclusive evidence at the present time that aspirin is effective in patients with coronary artery artery disease. Dipyridamole in combination with oral anticoagulants is effective in reducing the frequency of systemic embolism in patients with prosthetic heart valve replacement but is ineffective in patients with transient cerebral ischemic attacks or for the prevention of venous thromboembolism. Hydroxychloroquine was effective in reducing postoperative venous thrombosis in patients undergoing general abdominothoracic surgery but the evidence that it was effective in patients undergoing orthopaedic surgery is inconclusive. Sulphinpyrazone may be effective in reducing the frequency of sudden cardiac deaths in patients in the first year after myocardial infarction when it is started within 25 to 35 days after the infarction. Sulphinpyrazone reduced the incidence of arteriovenous shunt thrombosis in patients undergoing chronic hemodialysis and in combination with anticoagulants, it reduced the frequency of recurrent venous thrombosis. There have been no large scale trials of platelet suppressant drugs in clinical cancer and successful treatment of thromboembolic disorders cannot be used to predict success in the treatment of malignant disease.

Aspirin↗

PubMed2004

Acquiring and inhibiting prepotent responses in schizophrenia: event-related brain potentials and functional magnetic resonance imaging.

BACKGROUND: Schizophrenia is associated with deficits in using context to establish prepotent responses in complex paradigms and failures to inhibit prepotent responses once established. OBJECTIVE: To assess prepotent response establishment and inhibition in patients with schizophrenia using event-related brain potential (ERP) and functional magnetic resonance imaging (fMRI) in a simple NoGo task. To combine fMRI and ERP data to focus on fMRI activations associated with the brief (approximately 200 ms) moment of context updating reflected in the NoGo P300 ERP component. DESIGN AND SETTING: We collected ERP and fMRI data while subjects performed a NoGo task requiring a speedy button press to X stimuli (P=.88) but not to K stimuli (P=.12). The ERPs were collected at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif; fMRIs were collected at Stanford University, Stanford, Calif. PARTICIPANTS: We recruited patients with DSM-IV schizophrenia (n=11) from the community and the VA hospital and sex- and age-matched healthy control subjects (n=11) from the community. MAIN OUTCOME MEASURES: Behavioral accuracy, P300 amplitudes and latencies, and fMRI activations suggested that patients with schizophrenia did not establish as strong a prepotent tendency to respond to the Go stimulus as healthy subjects. In healthy subjects, NoGo P300 was related to activations in the anterior cingulate cortex, dorsal lateral prefrontal cortex, and right inferior parietal lobule and caudate nucleus, perhaps reflecting conflict experienced when withholding a response, control needed to inhibit a response, and stopping a response in action, respectively. In patients with schizophrenia, NoGo P300 was modestly related to activations in the anterior cingulate cortex, which is consistent with experiencing conflict. CONCLUSIONS: The difference in ERP and fMRI responses to Go and NoGo stimuli suggested that inhibiting a response was easier for patients with schizophrenia than for healthy subjects. Correlations of P300 and fMRI data suggested that patients with schizophrenia and healthy subjects used different neural structures to inhibit responses, with healthy subjects using a more complex system.

Adult↗

PubMed2005

Assessing the spatiotemporal evolution of neuronal activation with single-trial event-related potentials and functional MRI.

The brain acts as an integrated information processing system, which methods in cognitive neuroscience have so far depicted in a fragmented fashion. Here, we propose a simple and robust way to integrate functional MRI (fMRI) with single trial event-related potentials (ERP) to provide a more complete spatiotemporal characterization of evoked responses in the human brain. The idea behind the approach is to find brain regions whose fMRI responses can be predicted by paradigm-induced amplitude modulations of simultaneously acquired single trial ERPs. The method was used to study a variant of a two-stimulus auditory target detection (odd-ball) paradigm that manipulated predictability through alternations of stimulus sequences with random or regular target-to-target intervals. In addition to electrophysiologic and hemodynamic evoked responses to auditory targets per se, single-trial modulations were expressed during the latencies of the P2 (170-ms), N2 (200-ms), and P3 (320-ms) components and predicted spatially separated fMRI activation patterns. These spatiotemporal matches, i.e., the prediction of hemodynamic activation by time-variant information from single trial ERPs, permit inferences about regional responses using fMRI with the temporal resolution provided by electrophysiology.

Adult↗

PubMed1997

Obstruction of the fetal urinary tract.

Understanding the mechanisms of fetal obstructive uropathy will be essential for the specific management of the wide clinical spectrum of congenital obstructive conditions, including selecting observational therapy for mild cases and attempting to maximize renal function in severe cases. Recognition of the unique aspects of fetal renal obstruction is essential to formulate a useful research program, as the lessons of postnatal acquired obstruction are not directly transferable to congenital obstruction. Experimental studies of renal obstruction have demonstrated alterations in the developmental regulation of growth and differentiation in the fetal kidney. Depending on the gestational timing and severity of obstruction, growth may be impaired or accelerated. Similarly, patterns of altered differentiation may indicate immaturity or accelerated maturation, as well as aberrant differentiation. Concomitant with altered development, there is evidence that normal renal regulatory mechanisms, including the renin-angiotensin system and renal hemodynamics, may be affected by obstruction, possibly as compensatory responses. The mechanisms of these various alterations remain to be defined, but are likely to involve combinations of biomechanical signal transduction, growth factor expression, and responses of specific renal autoregulatory mechanisms. Fetal renal obstruction remains incompletely defined. The body of experimental evidence indicates that investigation of mechanisms regulating growth and differentiation is likely to yield important understanding of fetal renal obstruction to permit more accurate prognosis and management. Viewing fetal renal obstruction as a disorder of kidney development, with disordered growth and differentiation, suggests a definition of obstruction as a condition, that--if uncorrected--will lead to impairment in the ultimate functional potential of the kidney. Intervention should aim to maximize functional potential rather than to simply maintain the status quo.

Animals↗

PubMed1998

Prebiotics and synbiotics: concepts and nutritional properties.

The main role of diet is to provide enough nutrients to meet the requirements of a balanced diet, while giving the consumer a feeling of satisfaction and well-being. The most recent knowledge in bioscience supports the hypothesis that diet also controls and modulates various functions in the body, and, in doing so, contributes to the state of good health necessary to reduce the risk of some diseases. It is such an hypothesis which is at the origin both of the concept of 'functional food' and the development of a new scientific discipline of 'functional food science'. In the context of this paper the potential 'functional foods' to be discussed are the prebiotics and the synbiotics. The prebiotics developed so far are the non-digestible oligosaccharides and especially the non-digestible fructans among which chicory fructans play a major role. The chicory fructans are beta (2-1) fructo-oligosaccharides classified as natural food ingredients. They positively affect various physiological functions in such a way that they are already or may, in the future, be classified as functional food ingredients for which claims of functional effects or of disease risk reduction might become authorized. They are classified as prebiotic and have been shown to induce an increase in the number of bifidobacteria in human faecal flora. As part of a synbiotic-type product, they are already bifidogenic at a dose of 2.75 g/d and the effect lasts for at least 7 weeks. The other potential functional effects are on the bioavailability of minerals, but also, and more systemically, on the metabolism of lipids. Potential health benefits may concern reduction of the risk of intestinal infectious diseases, cardiovascular disease, non-insulin-dependent diabetes, obesity, osteoporosis and cancer. However, except for the prebiotic effect, and tentatively the improvement of calcium bioavailability, the evidence to support such effects is still missing in humans though hypotheses already exist to justify nutrition studies.

Bifidobacterium↗

PubMed1992

Effects of hormonal supplements on the maintenance of cardiac function in potential donor patients after cerebral death.

It is well-known that cardiac function in cerebrally dead patients rapidly deteriorates, leaving the organ unfit for donation. This study investigated whether or not cardiac function in patients with cerebral death can be maintained in a desirable condition with hormonal supplementation. In studies of changes in hormones before and after cerebral death, insulin, glucagon, triiodothyronine, thyroxine, cortisol, vasopressin, epinephrine, and norepinephrine values were measured with a lapse of time after cerebral death. Among them, triiodothyronine and cortisol levels were markedly reduced after cerebral death; therefore, these two hormones were selected as hormonal supplements. The average period from the judgment of cerebral death to cardiac arrest was 4.3 days in 12 patients with no hormonal supplement (group I) and more than 11.5 days in 4 patients with hormonal supplement (group II). This period for patients in group II was significantly longer (p less than 0.05). In 2 of the group II patients the hormonal supplementation was discontinued at the family's request, and in the other 2 patients, it was discontinued because of proposed renal donation. Hemodynamic comparisons between the two groups showed that the mean arterial pressure and the left ventricular maximum dp/dt were significantly higher (p less than 0.01) as was the cardiac index (p less than 0.05) on the 3rd day after cerebral death in members of group II. Thereafter, in group II, an excellent hemodynamic state was maintained until hormonal supplements were discontinued. We conclude that the triiodothyronine and cortisol supplements were effective in the maintenance of cardiac function in patients after cerebral death.

Adolescent↗

PubMedDate not supplied

Taurine: retinal function.

The status and potential functions of taurine in the retina have been reviewed. Taurine is present in high concentrations in the retina of all species tested, while the retinal concentrations of the enzymes necessary to synthesize taurine are presumed to vary among those species. The documented low activity of cysteinesulfinic acid decarboxylase, a key enzyme in taurine biosynthesis, in the livers of the cat, monkey and human possibly reflect low activity in their retinas, indicating reliance on the diet as an important source of taurine. Both high- and low-affinity binding proteins and uptake systems have been described for taurine in retinal tissue. Evoked release of taurine by light and other depolarizing stimuli have been well documented. Retinal pathologies including diminished ERGs and morphologic changes have been reported for animals and man deficient in taurine. Possible functions for taurine in the retina include: (1) protection of the photoreceptor - based on the shielding effects of taurine on rod outer segments exposed to light and chemicals; (2), regulation of Ca2+ transport - based on the modulatory effects of taurine on Ca2+ fluxes in the presence and absence of ATP; and (3) regulation of signal transduction - based on the inhibitory effects of taurine on protein phosphorylation.

Animals↗

PubMed2007

Evaluating the spatial relationship of event-related potential and functional MRI sources in the primary visual cortex.

The integration of electroencephalogram (EEG) recordings and functional magnetic resonance imaging (fMRI) can provide considerable insight into brain functionality. However, the direct relationship between neural and hemodynamic activity is still poorly understood. Of particular interest is the spatial correspondence between event-related potential (ERP) and fMRI sources. In the current study we localized sources generated by a checkerboard stimulus presented to eight subjects using both EEG and fMRI. The location of the sources of the visual evoked potential (VEP) were estimated at each timepoint and compared to the location of peak fMRI activity. In the majority of participants we found that the N75 dipole location coincides with a region of positive blood oxygenation level-dependent (BOLD) activation and the P100 dipole location coincides with a region of negative BOLD activation. These findings demonstrate the importance of including the negative BOLD response in combined EEG/fMRI studies.

Adult↗

PubMed2000

Distribution and potential biologic function of the thrombin receptor PAR-1 on human keratinocytes.

Thrombin has recently been shown not only to exert procoagulant activities, but also to induce mitogenic responses of different cell types involved in wound healing via binding to and cleavage of the thrombin receptor. In order to further explore these aspects of thrombin function, human keratinocytes (HaCaT cell line) were examined for their potential mitogenic responsiveness to thrombin and for the dependency of this process on the expression of the high-affinity thrombin receptor. Quiescent keratinocytes were stimulated in the mitogenic assay with alpha-thrombin and the thrombin receptor activating peptides TRAP42-55 (SFLLRNPNDKYEPY) and TRAP42-46 (SFLLR). A strong induction of cell proliferation was noted with alpha-thrombin, TRAP42-55 and TRAP42-46, but not with the "scrambled" peptide (FSLLR). These findings confirm that keratinocytes express the thrombin receptor and that the sequence of the first two amino acids of the generated neo-N-terminus are important for the activation of the receptor. Using cDNA fragments of the 5' coding sequence of the receptor, Northern blot analysis confirmed that HaCaT keratinocytes express the thrombin receptor. Expression of the receptor was also detected on normal human keratinocytes by immunohistochemistry and in situ hybridization. These data demonstrate the expression and biologic function of the human thrombin receptor on human keratinocytes, suggesting that thrombin, among other mediators, plays an important part in the orchestration of epidermal growth and repair processes.

Blotting, Northern↗

PubMed1987

Relationship among function, phenotype, and specificity in primary allospecific T cell populations: identification of phenotypically identical but functionally distinct primary T cell subsets that differ in their recognition of MHC class I and class II allodeterminants.

The goal of the present study was to evaluate the relationship among function, Lyt phenotype, and MHC recognition specificity in primary allospecific T cell populations. By using Lyt-2+ and L3T4+ T cells obtained from the same responder populations, we assessed the ability of T cells of each phenotype to generate cytotoxic effector cells (CTL) and IL 2-secreting helper T cells in response to either class I or class II MHC allodeterminants. It was found that a discordance between Lyt phenotype and MHC recognition specificity does exist in primary allospecific T cells, but only in one T cell subpopulation with limited functional potential: namely, Lyt-2+ T cells with cytotoxic, but not helper, function that recognize class II MHC alloantigens. Target cell lysis by these Lyt-2+ class II-allospecific CTL was inhibited by anti-Ia monoclonal antibodies (mAb), but not anti-Lyt-2 mAb, indicating that they recognized class II MHC determinants as their "restriction" specificity and not as their "nominal" specificity even though they were Lyt-2+. A second allospecific T cell subset with limited functional potential was also identified but whose Lyt phenotype and MHC restriction specificity were not discordant: namely, an L3T4+ T cell subset with helper, but not cytotoxic, function specific for class I MHC allodeterminants presented in the context of self-Ia. Thus, the present study demonstrates that primary allospecific T cell populations contain phenotypically identical subpopulations of helper and effector cells that express fundamentally different MHC recognition specificities. Because the recognition specificities expressed by mature T cells reflect the selection pressures they encountered during their differentiation into functional competence, these findings suggest that functionally distinct but phenotypically identical T cell subsets may be selected independently of one another during ontogeny. Thus, the existence of Lyt-2+ CTL specific for class II allodeterminants can be explained by the hypothesis that the association of Lyt phenotype with MHC recognition specificity results from the process of thymic selection that these Lyt-2+ effector cells avoid.

Animals↗