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PubMed1992

The role of cytosolic Ca2+ in cell injury, necrosis and apoptosis.

Increases in cytosolic Ca2+ are believed to be a pivotal signal in the regulation of cell injury, cell death, cell proliferation, cellular differentiation and cellular aging. Changes in the concentration of cytosolic Ca2+ are involved in both acute and chronic cell injury, as well as in accidental or programmed cell death. Signalling in all of these phenomena is dependent on mediated activities of a number of intracellular factors, including phospholipases, proteases and endonucleases. The coordinate regulation of these factors, as well as of oncogene activation, seems to play a role both in the processes of cell injury and cell death, and in the recovery from injury in sublethally injured cells.

Animals↗

PubMed2005

The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina.

In this work we advance the hypothesis that omega-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) exhibit cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. omega-3 LCPUFAs may modulate metabolic processes and attenuate effects of environmental exposures that activate molecules implicated in pathogenesis of vasoproliferative and neurodegenerative retinal diseases. These processes and exposures include ischemia, chronic light exposure, oxidative stress, inflammation, cellular signaling mechanisms, and aging. A number of bioactive molecules within the retina affect, and are effected by such conditions. These molecules operate within complex systems and include compounds classified as eicosanoids, angiogenic factors, matrix metalloproteinases, reactive oxygen species, cyclic nucleotides, neurotransmitters and neuromodulators, pro-inflammatory and immunoregulatory cytokines, and inflammatory phospholipids. We discuss the relationship of LCPUFAs with these bioactivators and bioactive compounds in the context of three blinding retinal diseases of public health significance that exhibit both vascular and neural pathology. How is omega-3 LCPUFA status related to retinal structure and function? Docosahexaenoic acid (DHA), a major dietary omega-3 LCPUFA, is also a major structural lipid of retinal photoreceptor outer segment membranes. Biophysical and biochemical properties of DHA may affect photoreceptor membrane function by altering permeability, fluidity, thickness, and lipid phase properties. Tissue DHA status affects retinal cell signaling mechanisms involved in phototransduction. DHA may operate in signaling cascades to enhance activation of membrane-bound retinal proteins and may also be involved in rhodopsin regeneration. Tissue DHA insufficiency is associated with alterations in retinal function. Visual processing deficits have been ameliorated with DHA supplementation in some cases. What evidence exists to suggest that LCPUFAs modulate factors and processes implicated in diseases of the vascular and neural retina? Tissue status of LCPUFAs is modifiable by and dependent upon dietary intake. Certain LCPUFAs are selectively accreted and efficiently conserved within the neural retina. On the most basic level, omega-3 LCPUFAs influence retinal cell gene expression, cellular differentiation, and cellular survival. DHA activates a number of nuclear hormone receptors that operate as transcription factors for molecules that modulate reduction-oxidation-sensitive and proinflammatory genes; these include the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and the retinoid X receptor. In the case of PPAR-alpha, this action is thought to prevent endothelial cell dysfunction and vascular remodeling through inhibition of: vascular smooth muscle cell proliferation, inducible nitric oxide synthase production, interleukin-1 induced cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production. Research on model systems demonstrates that omega-3 LCPUFAs also have the capacity to affect production and activation of angiogenic growth factors, arachidonic acid (AA)-based vasoregulatory eicosanoids, and MMPs. Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a family of eicosanoids that have the potential to affect AA-derived eicosanoids implicated in abnormal retinal neovascularization, vascular permeability, and inflammation. EPA depresses vascular endothelial growth factor (VEGF)-specific tyrosine kinase receptor activation and expression. VEGF plays an essential role in induction of: endothelial cell migration and proliferation, microvascular permeability, endothelial cell release of metalloproteinases and interstitial collagenases, and endothelial cell tube formation. The mechanism of VEGF receptor down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa B (NFkappaB). NFkappaB is a nuclear transcription factor that up-regulates COX-2 expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase. All four factors are associated with vascular instability. COX-2 drives conversion of AA to a number angiogenic and proinflammatory eicosanoids. Our general conclusion is that there is consistent evidence to suggest that omega-3 LCPUFAs may act in a protective role against ischemia-, light-, oxygen-, inflammatory-, and age-associated pathology of the vascular and neural retina.

Adolescent↗

PubMed2004

Adult Burkitt leukemia and lymphoma.

The World Health Organization Classification of Lymphoid Neoplasms identifies Burkitt lymphoma/leukemia as a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants. These subtypes share many morphologic and immunophenotypic features, but differences exist in their clinical and geographic presentations. All of these subtypes possess chromosomal rearrangements of the c-myc oncogene, the genetic hallmark of Burkitt lymphoma that contributes to lymphomagenesis through alterations in cell cycle regulation, cellular differentiation, apoptosis, cellular adhesion, and metabolism. Brief-duration, high-intensity chemotherapy regimens containing aggressive central nervous system prophylaxis have had remarkable success in the treatment of this disease, with complete remission rates of 75% to 90% and overall survivals reaching 50% to 70% in adults. Although Burkitt lymphoma cells are extremely chemosensitive, biologically targeted therapies should be developed because current treatment options are suboptimal for patients with poor prognostic features or in the setting of relapsed disease.

Adult↗

PubMed1996

Maturation of intracranial immature teratomas. Report of two cases.

Immature teratomas arising within the central neuraxis are rare neoplasms. These tumors contain diverse cell lineages that retain an embryonal character and display phenotypic differentiation attributed to the three classic germ layers. The clinical management of these lesions is unclear, due in part to their low incidence and to an incomplete understanding of their natural history. Although the potential for phenotypic differentiation and cellular maturation within immature teratomas arising in the gonads is well documented, this has not been described in the intracranial tumors. In the present report, the authors describe two cases of intracranial immature teratomas, one involving the pineal region and the other involving the left frontotemporal lobes, which underwent cellular differentiation and maturation. At initial resection, the tumors from both cases were composed predominantly of primitive neuroepithelial tissue that was admixed with immature and differentiating mesenchymal and epithelial structures. No foci of germinoma, endodermal sinus, choriocarcinoma, or embryonal carcinoma tissue were present. Subsequent resections in both cases revealed an absence of immature tissue. The tumor in Case 1 contained only differentiated epithelial and mesenchymal tissue with no neuroepithelial component, whereas the tumor in Case 2 demonstrated abundant mature neuronal and glial tissue. These two cases from different intracranial sites suggest that spontaneous maturation may be a significant aspect of the natural history of intracranial immature teratomas.

Brain Neoplasms↗

PubMed1992

[Teratology and epidemiology in the study of environmental teratogens].

The processes of cellular migration, cellular differentiation and cellular multiplication are studied, since these are the basic developmental processes upon which teratogenic agents act resulting in congenital malformations. We also carefully analyze the interactions between teratogen-embryo in order to establish adequate parameters for analysis of environmental teratogens, as well as experimental teratogenesis and epidemiology. Information on the pathogenesis of congenital malformations obtained from experimental teratology in an adequate biological model, can be extrapolated to the human. The etiology of congenital malformations resulting from environmental teratogens can only be elucidated through epidemiology, since there is species specificity. Such a study must fulfill the following prerequisites: diagnosis of the congenital malformation, ruling out genetic factors in the family tree and determination of the exact time of exposure to the possible teratogen during the pregnancy.

Abnormalities, Drug-Induced↗

PubMed2006

HPSE-1 expression and functionality in differentiating neural cells.

The study of cellular differentiation encompasses many vital parts of biology and medicine. Heparan sulfate proteoglycans (HSPG) are essential and ubiquitous macromolecules associated with the cell surface and extracellular matrix (ECM) of a wide range of cells and tissues. Heparan sulfate chains (HS) of HSPG bind and sequester a multitude of extracellular ligands, including growth factors, cytokines, chemokines, enzymes, and lipoproteins. Enzymatic degradation of HS is therefore involved in processes such as cell proliferation, migration, and differentiation. Heparanase (HPSE-1) is an HS degradative enzyme associated with inflammation and lipid metabolism and is a critical molecular determinant in cancer metastasis. The enzyme acts as an endo-beta-D-glucuronidase, which degrades HS at specific intrachain sites, resulting in HS fragments of discrete molecular weights that retain biological function. HPSE-1's relevance as the only example of cloned/purified mammalian HS degradative enzyme led us to investigate its functionality in human olfactory epithelium (HOE) cells as a paradigm for HPSE-1's roles in neural cell differentiation. We provide the first evidence of 1) HPSE-1 presence in HOE cells and 2) a highly significant increase of HPSE-1 mRNA and enzyme activity in differentiating vs. proliferating HOE cells. Our data suggest that an augmented HPSE-1 activity may represent a physiological mechanism involved in neural cellular differentiation.

Cell Differentiation↗

PubMed1991

Electron microscopy of Coxiella burnetii in tissue culture. Induction of cell types as products of developmental cycle.

An in vitro ultrastructural study was carried out on tissue cultures (J774, murine macrophage-like tumour cell line, and BHK-21, baby hamster kidney cell line) persistently infected with C. burnetii to investigate whether the events of cellular differentiation could be visualized. At a given stage of the developmental cycle, a proportion of the cells within the affected phagolysosomes clearly underwent cellular differentiation. The cells initially showed asymmetrical septation, the primary stage of cellular differentiation, and ended with the formation of the differentiated product, a precursor to the small cell. The results verified our initial observation that the events occurring during growth in a phagolysosome represent stages of a complex developmental cycle consisting not only of i) vegetative growth by typical transverse binary fission, but also ii) cellular differentiation.

Animals↗

PubMed2005

[Gallbladder adenocarcinoma: tumoral staging, histological prognostic factors and survival].

INTRODUCTION: Gallbladder adenocarcinoma is an aggressive tumor and is one of the digestive tract malignancies with the poorest prognosis. Because of loco-regional extension and delayed diagnosis, curative resection is often impossible. To determine histological prognostic factors and survival in relation to tumoral stage at diagnosis, we performed a retrospective study of our patients with gallbladder carcinoma. PATIENTS AND METHOD: Sixty-two patients with gallbladder adenocarcinoma diagnosed over a 15-year period were retrospectively included in this study. The surgical procedures performed in this group of patients were laparoscopic cholecystectomy, open cholecystectomy and palliative surgery in patients with unresectable tumors. For each tumoral stage, age, sex, cellular differentiation, tumor size, the presence of metastatic nodes, histological variables linked to poor prognosis, and survival were compared. RESULTS: Of the 62 patients included, 45 were women and 17 were men. The mean age was 75 years. No significant differences were found in relation to age or sex among the different tumoral stages. Cellular differentiation and survival were poorer with advanced tumoral stage. A significant predominance of histological factors of poor prognosis was found in T2 and T3 tumors. CONCLUSIONS: Preoperative diagnosis of gallbladder adenocarcinoma is difficult except in advanced cases. It is often incidentally diagnosed at histological examination of gallbladders, and shows little local advancement and a good degree of cellular differentiation. The etiology of this tumor is unknown but its prevalence is greater among women. Clinical symptoms are similar to those caused by gallstones. In this study no relationship was found between age and sex and tumoral stage. In advanced tumoral stages poor cellular differentiation is predominant as well as other histological markers of poor prognosis. Good survival was found in T3 tumors, possibly linked to good cellular differentiation. Due to high associated comorbidity, none of the patients underwent reintervention.

Adenocarcinoma↗

PubMed2003

Herpetomonas samuelpessoai: dimethylsulfoxide-induced differentiation is influenced by proteinase expression.

In this study, we analyzed the influence of proteinase expression on the cellular differentiation of Herpetomonas samuelpessoai. Along cellular differentiation, which was induced by dimethylsulfoxide (DMSO), the trypanosomatids secreted several molecules with variable proteolytic activity. All of them were inhibited by 10 m M 1,10-phenanthroline, suggesting that they are zinc-metalloproteinases. Analysis of parasite extracts revealed the occurrence of a 63-kDa metalloproteinase and a 45-kDa cysteine proteinase. After extraction with Triton X-114 followed by water-detergent partition, the 63-kDa component was present in both aqueous and detergent phases, which indicated that this enzyme may be distributed over different cellular compartments including membrane domains. The 45-kDa component, however, presented hydrophilic properties and was predominantly expressed by DMSO non-treated parasites, suggesting that proteinases may be involved in the process of cellular differentiation in H. samuelpessoai. This was confirmed by the fact that a cysteine proteinase inhibitor abrogated parasite differentiation. The role of proteinases and their relevance in the differentiation of H. samuelpessoai are discussed.

Animals↗

PubMed1998

Mathematical modeling of biofilm structure with a hybrid differential-discrete cellular automaton approach.

A hybrid differential-discrete mathematical model has been used to simulate biofilm structures (surface shape, roughness, porosity) as a result of microbial growth in different environmental conditions. In this study, quantitative two- and three-dimensional models were evaluated by introducing statistical measures to characterize the complete biofilm structure, both the surface structure and volume structure. The surface enlargement, coefficient of roughness, fractal dimension of surface, biofilm compactness, and solids hold-up were found to be good measures of biofilm structure complexity. Among many possible factors affecting the biofilm structure, the influence of biomass growth in relation to the diffusive substrate transport was investigated. Porous biofilms, with many channels and voids between the "finger-like" or "mushroom" outgrowth, were obtained in a substrate-transport-limited regime. Conversely, compact and dense biofilms occurred in systems limited by the biomass growth rate and not by the substrate transfer rate. The surface complexity measures (enlargement, roughness, fractal dimension) all increased with increased transport limitation, whereas the volume measures (compactness, solid hold-up) decreased, showing the change from a compact and dense to a highly porous and open biofilm.

Automation↗

PubMed2000

Temporal variations in protein tyrosine phosphatase activity during cell proliferation and differentiation.

Cellular oscillations in total extractable protein content and protein tyrosine phosphatase activity were analysed in proliferating and differentiating human acute promyelocytic leukaemic (HL-60) cell extracts. Differentiation was induced along the granulocytic pathway using all-trans retinoic acid (ATRA). High frequency rhythms with distinct, well defined waveforms of varying amplitude were observed for both the total protein content and for the enzyme activity of protein tyrosine phosphatase (PTP). Linear correlation analysis showed that there was no obvious relationship between the protein content and the corresponding PTP activity, suggesting that the periodic variations between these two components are relatively independent of each other. ATRA significantly altered the characteristics of the rhythms with respect to the period and amplitude and had a dampening effect on the oscillatory pattern of PTP activity. Modulation of such characteristics may be of significance with respect to the regulation of the differentiation processes and the possible reversal of transformation.

Cell Differentiation↗

PubMed1997

Nuclear lamin expression in normal testis and testicular germ cell tumours of adolescents and adults.

Nuclear A- and B-type lamins are differentially expressed in tissues, depending on the degree of cellular differentiation and proliferative status. By studying lamin expression in testis parenchyma and testicular germ cell tumours, further insight may be gained into the degree of cellular differentiation in normal testis and into the whole spectrum of differentiation lineages found in testicular germ cell tumours. Frozen tissue sections of normal testis and the different types of testicular germ cell tumours were immunostained with monoclonal antibodies to distinct lamin subtypes. Lamin reactivity was evaluated in relation to the lineage and degree of cellular differentiation and the reactivity patterns were compared with each other and with those in normal testis. In normal testis, both A- and B-type lamins were expressed in Sertoli, Leydig, and peritubular cells, while in spermatogonia only B-type lamins were found and spermatocytes showed weak reactivity with the A-type lamin antibodies. Carcinoma in situ was most often positive for both of the B-type lamins and negative for the A-type lamins (lamins A and C). In testicular germ cell tumours, B-type lamins were always expressed, while A-type lamins were differentially expressed. Differentiated non-seminomas were positive for both of the A-type lamins, whereas embryonal carcinomas were positive for lamin C and negative for lamin A. Seminomas were negative for both of the A-type lamins, with the exception of seminomas containing a Ras mutation. Spermatogonia and seminoma cells, which follow a differentiation pathway along the spermatogenic lineage and show characteristics of germ cells, do not express A-type lamins. Non-seminomas, showing embryonal or extraembryonal differentiation, express A-type lamins to varying degrees, distinguishing embryonal carcinoma cells from other non-seminomatous components. This may aid in the evaluation of the percentage of embryonal carcinoma in non-seminomatous testicular germ cell tumours as a prognostic parameter.

Adolescent↗

PubMed1998

The role of globo-series glycolipids in neuronal cell differentiation--a review.

Alterations in glycolipid composition as well as glycosyltransferase activities during cellular differentiation and growth have been well documented. However, the underlying mechanisms for the regulation of glycolipid expression remain obscure. One of the major obstacles has been the lack of a well defined model system for studying these phenomena. We have chosen PC12 pheochromocytoma cells as a model because (a) the properties of these cells have been well characterized, and (b) they respond to nerve growth factor (NGF) by differentiating into sympathetic-like neurons and are amenable to well-controlled experimentation. Thus, PC12 cells represent a suitable model for studying changes in glycolipid metabolism in relation to cellular differentiation. We have previously shown that subcloned PC12 cells accumulate a unique series of globo-series neutral glycolipids which are not expressed in parental PC12 cells. This unusual change in glycolipid distribution is accompanied by changes in the activities of specific glycosyltransferases involved in their synthesis and is correlated with neuritogenesis and/or cellular differentiation in this cell line. We have further demonstrated that changes in the glycosyltransferase activities may be modulated by the phosphorylation states of the cells via protein kinase systems. We conclude that these unique globo-series glycolipids may play a functional role in the initiation and/or maintenance of neurite outgrowth in PC12 cells.

Animals↗

PubMed2004

Use of an automated hematology analyzer and flow cytometry to assess bone marrow cellularity and differential cell count.

The automated analysis of bone marrow aspirates was performed to estimate the bone marrow cellularity and differential cell count. Total nucleated cell count (TNC) was measured using an automated hematology analyzer. TNC of the bone marrow correlated well with the bone marrow cellularity estimated by microscopic examination (r = 0.590, p <0.001). The bone marrow cellularity was readily confirmed as <30%, from 30 to 70%, or >70% according to TNC. Differential count of bone marrow cells was done with the combination of CD45 monoclonal antibody and propidium iodide using flow cytometry. Excellent correlations were obtained for the population distributions of normoblasts, eosinophils, lymphocytes, and blasts between the results of flow cytometry and manual differential counts. The percentage of mature granulocytes in flow cytometry showed good correlation with the manual percentage of metamyelocytes + neutrophils. The percentage of immature granulocytes by flow cytometry showed good correlation with the manual percentage of blasts + promyelocytes + myelocytes. These results demonstrate that analysis of bone marrow aspirates using an automated hematology analyzer is valuable in the determination of bone marrow cellularity. Moreover, as flow cytometry provides objective findings for percentages of major cell populations, it can serve as a method to automate bone marrow differentials.

Antigens, CD↗

PubMed1989

Receptor glycosylation regulates the affinity of histamine H1 receptors during smooth muscle cell differentiation.

During the cellular differentiation of the cultured smooth muscle cells, BC3H1, the Kd and the number of binding sites for [3H]-pyrilamine were decreased transiently from 276 nM to 46.5 nM and from 13.3 x 10(6)/cell to 2 x 10(6) cell, respectively. Concanavalin A (Con-A), wheat germ agglutinin, and lentil lectin inhibited [3H]pyrilamine binding to differentiated BC3H1 cells but not to undifferentiated cells. The [3H]pyrilamine binding activity of digitonin-solubilized membranes from differentiated cells was successively recovered from Con-A agarose affinity chromatography but not from undifferentiated cell membranes. The glycosylation inhibitors tunicamycin and swainsonine inhibited the expression of high affinity pyrilamine binding sites during BC3H1 cell differentiation. The molecular weight of high affinity [3H]pyrilamine binding sites on differentiated cells were approximately 68,000 as analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, which after treatment with N-glycanase was shifted to 40,000, a molecular weight similar to that of low affinity [3H]pyrilamine binding sites on undifferentiated cells. These data suggest that one element contributing to H1-receptor heterogeneity is receptor-N-glycosylation.

Alkaloids↗

PubMed1995

Cell cycle gene expression and E2F transcription factor complexes in human melanoma cells induced to terminally differentiate.

Defects in cellular differentiation are a common occurrence in human cancers. The combination of recombinant human fibroblast interferon (IFN-beta) and the antileukemic compound mezerein (MEZ) results in an irreversible loss of proliferative capacity and terminal cell differentiation in H0-1 human melanoma cells. In contrast, either agent alone induces reversible growth arrest and/or specific components of the differentiation process without inducing terminal differentiation. The current study investigates changes in cell cycle, cell cycle gene expression and E2F transcription factor complex formation during the processes of reversible and irreversible (terminal) differentiation. Induction of both terminal differentiation and reversible differentiation (MEZ treatment) results in a temporal decrease in DNA synthesis and the percentage of cells in S phase and a decrease in the expression of cell cycle and growth regulated genes, including cdc2, cyclin A, cyclin B, histone H1, histone H4, nm23-H1, p53 and c-myc. Persistent gene expression changes occur in terminally differentiated cells, but not in reversibly differentiated cells. H0-1 cells contain several E2F binding activities, including uncomplexed E2F, an E2F-p107-cyclin A-cdk2 kinase complex and an Rb-E2F complex. Induction of growth arrest by MEZ results in a slow migrating gelshift band that contains E2F associated with the pRb2/p130 protein. There is also a loss of the Rb-E2F complex. Induction of terminal differentiation after treatment with IFN-beta + MEZ generates a second pRb2/p130-E2F complex that migrates considerably faster than the pRb2/p130-E2F complex resulting from growth arrest. The slower migrating complex may contribute to growth arrest, whereas the faster migrating complex may play a role in terminal differentiation. Our results demonstrate that terminal cell differentiation involves a co-ordinate and continuous suppression of a number of cell cycle and growth related genes and results in the development of a novel E2F transcription factor complex not apparent in growth arrested and reversibly differentiated human melanoma cells.

CDC2 Protein Kinase↗

PubMed1995

Expression of p68 in human colon cancer.

p68 is an interferon-inducible protein kinase which is a key factor in the regulation of both viral and cellular protein synthesis. Since p68 plays a central role in cellular protein synthesis, we hypothesized that it would parallel translational activity, and thereby correlate with cellular differentiation in both normal and neoplastic cell types. Using the anti-p68 monoclonal antibody, TJ4C4, we have previously noted a correlation of p68 expression with the degree of cellular differentiation in the human upper aerodigestive tract and lung. During normal human fetal development, p68 is abundantly expressed in the upper aerodigestive tract and lungs, but considerably less so in the colon. In order to determine if this fetal expression pattern correlated with the pattern seen in adult colon and colonic adenocarcinomas, we analyzed the expression pattern of p68 in 80 patients with adenocarcinoma of the colon. Using light microscopic evaluation of immunoperoxidase-stained tissue sections, a spectrum of p68 expression was noted among the tissue samples. Increased p68 levels were noted in the majority of tumors with increased cellular differentiation, and those tissues with decreased p68 were, in general, less differentiated. These data are consistent with the concept that the expression of p68 parallels the degree of cellular differentiation, and are consistent with previously reported studies using this antibody. The limited fetal expression pattern of p68 in the colon and the variable correlation of p68 with differentiation suggests that p68, as well as other translational regulators, can be important in assessing the biological potential of tumors arising in the colon.

Adenocarcinoma↗

PubMed1997

Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1.

The failure of immune effector mechanisms to control HIV-1 infection has important consequences for the human host. In a randomized cohort of HIV-infected patients, there was striking in vitro restriction of the proliferative response to HIV-1 envelope protein (Env), gp160; only 34% of patients recognized Env. Therapeutic vaccination with recombinant gp160 or gp120 (rgp160, rgp120) reversed the restriction in vitro, with Env recognition rising to 81%. Peripheral blood mononuclear cells (PBMC) from HIV-infected vaccine recipients, placebo recipients, and seronegative volunteers were cultured with exogenous IL-7 or IL-12 and either tetanus toxoid (TT) or gp160. IL-7 significantly augmented proliferative responses to TT and gp160, whereas IL-12 only affected proliferation to gp160. IL-7, but not IL-12, increased the number of HIV-infected placebo recipients who recognized rgp160. IL-12 had its greatest effect in the induction of rgp160-specific responses from seronegative individuals. The data suggest that these two cytokines have differential activity in the relief of restricted cellular immunity to Env; the predominant effect of IL-7 is in individuals who have been primed by exposure to antigen, while the effect of IL-12 is most evident in seronegative, unprimed individuals. Modification of restricted proliferative responses to Env by vaccination or cytokines in vitro suggests that strategies incorporating IL-7 or IL-12 as adjuvants may selectively boost cellular reactivity to HIV-1.

AIDS Vaccines↗