Coding sequence polymorphism of Tcrg-V1, -V2, and -V4 genes in mice bearing Tcr-gA and -gC haplotypes.
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Amino Acid Sequence↗
Biomedical subjects
T Roger
Publications and source records attributed to T Roger.
Negative segregation of Mtv loci in H-2E+ mice selected for high antibody response.
Endogenous mouse mammary tumor proviruses (Mtvs) encode superantigens (Sags), which can delete T lymphocytes expressing particular Tcrb-V genes when associated with the H-2E molecule. In the present work, distribution of Mtvs was investigated in six independent pairs of mouse lines genetically selected for high (H) or low (L) Ab production to specific T-cell-dependent Ags. These experiments were performed to evaluate the role of Mtv-encoded Sags in the determination of H and L phenotypes. No systematic difference is observed in Mtv segregation between H-2E- H and L mouse lines. However, a clear differential segregation of Mtv loci is observed between H-2E+ H and L mice from three independent selections. The number of endogenous Mtvs in L lines is close to that found in laboratory mice. In contrast, Mtv loci-encoding Sags are almost absent in H animals. Although Sags profoundly affect the available Tcrb-V repertoire in H-2E+ L mice, it seems unlikely that Mtvs account for the L phenotype which can be achieved independently of Mtv segregation in H-2E- lines. More importantly, the results suggest that negative segregation of Mtv-encoding Sags contribute to determine the super-responder phenotype of H lines.
Animals↗
A possible interaction between serotonin and cholecystokinin-8 in the ileo-colonic motor responses to feeding in rats.
The effects of cholecystokinin (CCK)-A, CCK-B, and 5-hydroxytryptamine-2 (5-HT2) receptor antagonists on the postprandial myoelectric activity of the ileum and the proximal and distal colon in rats were studied. After L364,718, a CCK-A receptor antagonist, or ritanserin, 5-HT2 receptor antagonist, the duration of the ileal postprandial motor pattern was reduced by 60%. In contrast, L365,260, a CCK-B receptor antagonist, had no effect. In the distal colon, the postprandial response was inhibited by CCK-A, CCK-B, and 5-HT2 receptor antagonists, whereas they were inactive in the proximal colon. CCK-8 administered at the end of the meal suppressed the inhibitory effect of ritanserin on the ileum and the distal colon. These results suggest that, in rats, CCK-8 is involved in the control of the ileal motor response to feeding through CCK-A receptors and in that of the distal colon through both CCK-A and CCK-B receptors. Serotonin seems to play a role in CCK-8 control through 5-HT2 receptors.
Animals↗
Comparative effects of mu and kappa opiate agonists on the cecocolic motility in the pony.
The electrical and mechanical activity of the large intestine and its response to administration of opiate mu and kappa agonists were assessed from electrodes and inductograph coils chronically implanted on the cecocolic segment in six ponies given a diet of hay and concentrates. Before the drugs were given, migrating complexes propagating from the cecum into the colon occurred at the rate of 1.5 to 16/hour. During this propulsive activity, the cecocolic sphincter opened and closed allowing the outflow of cecal contents and preventing the backflow of colic contents. Each pony was used as its own control and was given fentanyl (0.01 and 0.05 mg/kg of body weight, IV) and U50488H (0.1 and 0.5 mg/kg, IV) at weekly intervals. The mu agonist fentanyl elicited a marked phase of inhibition of the propulsive activity and a closure of the cecocolic sphincter that lasted one to two hours depending on the dose. The kappa agonist U50488H induced an inhibition of the short spiking activity, i.e. of the resting muscle tone. It did not disturb the occurrence of migrating complexes nor that of the openings of the cecocolic sphincter. These kappa compounds may be drugs of choice to alleviate visceral pain in colic stases without inducing delay of transit unlike mu compounds.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
Co-selection of the rare T cell receptor-gamma B haplotype in mouse lines selected for low responsiveness to red blood cell antigens.
T cell receptor (TcR)-gamma haplotype was investigated in seven pairs of murine Biozzi lines selected for low and high antibody (Ab) response to different antigens (Ag). High-responder lines (H) express gamma A or gamma C haplotypes irrespective of the selecting Ag. In contrast, the gamma B haplotype, which is rare in laboratory mouse strains, is found in all low-responder lines (L) to sheep erythrocyte Ag (SE). However, the TcR-gamma B locus might only have a low penetrance in the control of the SE response. Moreover, investigations using LIVA mice, which were selected for low SE response from homozygous gamma A founder parents, indicate that the gamma B haplotype is neither necessary nor sufficient to achieve a low-responder phenotype. The gamma B haplotype might, thus, be co-selected to confer to L mice an improved resistance to bacterial infections mediated by gamma delta T cells compensating the profound and nonspecific immune perturbation associated with the low Ab response.
Animals↗
New T-cell receptor gamma haplotypes in wild mice and evidence for limited Tcrg-V gene polymorphism.
Tcrg gene polymorphism was investigated by Southern blot analysis on a panel of laboratory and wild mouse strains using a set of probes which identify all known Tcrg-V and -C genes. Only three haplotypes are found in laboratory mice: gA, gB, and gC which are represented by BALB/c, AKR, and DBA/2 prototypes respectively. gA and gC haplotypes are the most frequent among laboratory mice whereas gB is poorly represented. Seven new haplotypes are described among 23 wild mice corresponding to four Mus musculus subspecies (Mus mus domesticus, castaneus, musculus, and molossinus). However, only a few new alleles of individual genes are observed. Tcrg-V genes located at the 5' end of the Tcrg locus (V7 and V4) appear to be nonpolymorphic whereas two Tcrg-V3, -V5, -V6, -C4 and three Tcrg-V1, -V2, -C1, -C2, and -C3 specific restriction fragment length polymorphisms are detected. These results indicate a relatively high degree of conservation of Tcrg genes as compared to other members of the immunoglogulin (Ig) gene family and might be related to the specifity and function of gamma delta T cells. Several of the new haplotypes described here result from point mutations in noncoding Tcrg-V or -C gene-flanking regions. Recombinations may have also participated in the evolution of the Tcrg locus. Finally, these new Tcrg haplotypes are unequally distributed among the four M. m. subspecies and support the idea that the gA and gC haplotypes found in laboratory mice are inherited from M. m. domesticus whereas gB might originate from asian subspecies (castaneus, musculus or molossinus).
Animals↗
Rearrangement by chromosomal inversion in the T cell receptor gamma locus in a murine alpha beta T cell clone.
Analyzing the T-cell receptor (TCR) repertoire of T lymphocytes specific for minor histocompatibility antigens, we isolated a TCR-alpha beta bearing T cell clone, TGVH9, which also expresses three different TCR-gamma mRNA. The sequences of these messengers indicate that one of them results from the rearrangement of V gamma 1 and J gamma 2 genes. Since these two segments are in inverted genomic transcriptional orientation, the joining of V gamma 1 to J gamma 2 occurred by chromosomal inversion. This mechanism, which was previously reported in TCR-beta and TCR-delta loci, can thus also occur to enlarge the diversity of the TCR-gamma repertoire.
Amino Acid Sequence↗
Preferential V delta 1 expression among TcR gamma/delta-bearing T cells in human oral epithelium.
The oral cavity is a septic area colonized by various bacterial species, and the oral mucosa is frequently submitted to microtraumas. Several mechanisms are implicated in the defence of the oral tissue, but little is known concerning the eventual presence and role of gamma/delta T cells at this site. Samples of healthy keratinized oral mucosa were examined with immunochemical techniques using anti-CD3, CD4, CD8, CD22, TcR delta 1, V delta 1 and V delta 2 monoclonal antibodies. Whatever the site examined, gamma/delta T cells represent at most 2% of the T-cell population, a value similar to that found in other tissues. In the connective tissue, under the basement membrane, V delta 2+ gamma/delta T cells are predominant whereas the epithelium mostly contains V delta 1+ gamma/delta T cells. The significance of this preferential V delta 1 intraepithelial presence is discussed.
B-Lymphocytes↗
Mls-1 and Mls-2 superantigens do not control susceptibility to collagen-induced arthritis in HI and HII mice.
The HI mouse line is sensitive to collagen-induced arthritis (CIA), whereas HII is refractory, although both express the H-2q permissive haplotype. The two lines also share the same T-cell receptor (TcR) gene haplotypes for alpha and beta chains. The distribution of mouse mammary tumour viruses (MMTV), which encode endogenous superantigens (SAg) such as minor leucocyte-stimulating antigens (Mls) known to modulate the available TcR-V beta repertoire, was investigated in the two lines. Mls-1 is present in HI-susceptible mice, while Mls-2 and Mls-2-like SAg are absent in both lines. This suggests that Mls antigens play no significant role in the resistance to CIA. Moreover, HI and HII exhibit close V beta gene usage as assessed by fluorescence staining with 11 V beta-specific monoclonal antibodies (mAb). These results indicate that mechanisms other than clonal deletion based on V beta expression and induced by SAg are involved in the resistance of H-2q-positive mice to experimental arthritis. Yet, a slightly reduced level of V beta 5+ T cells is observed in HII animals which might correlate with the presence of Mtv-6 and Mtv-9 proviruses.
Animals↗
Comparison of the repertoire of T-cell lines and clones specific for minor histocompatibility antigens derived from immunized mice and from mice developing a graft-versus-host reaction.
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Animals↗
Polymorphism of the Tcrg-V1-V2 region in mice: identification of a new Vg1 allele in DBA/2.
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Alleles↗
Resistance to collagen-induced arthritis in Biozzi mice is not associated with T cell receptor V beta gene polymorphism.
H-I and H-II high antibody-responder Biozzi mice, which express the H-2q permissive haplotype, were shown to be sensitive and refractory to collagen-induced arthritis, respectively. To assess a possible role of T cell receptor (TcR) V beta gene deletion or polymorphism in the resistance to arthritis in H-II mice, the germinal structure of TcR V beta genes and their expression at the membrane level were compared in both lines. In contrast to H-2q refractory SWR mice, which exhibit a deletion of about 50% of TcR V beta gene segments. H-I and H-II lines have an identical and complete set of V beta genes and exhibit no difference in the average expression of V beta 6, V beta 8 and V beta 11 gene products on T cell surface. These results indicate that mechanisms other than V beta gene deletion or polymorphism can be involved in the resistance of H-2q-positive mice to experimental arthritis.
Animals↗
[The microscopic and functional anatomy of the ileal papilla (papilla ilealis) and the cecocolic valve (valva caecocolia) and the pelvic flexure (flexura pelvina) of the horse (Equus caballus)].
The histologic study on six horses of the ileo-caecal and caeco-colic junctions confirms their sphincteral structure. It appears that the activity of the muscular fibres, identified in the ileo-caecal and caeco-colic plica, modulates the curvature of the junctions and thus, blocks, as sphincters, the reflux of contents from the caecum into the ileum and from the colon into the caecum. But on the other hand, the pelvic flexure does not possess any microscopic organization to stop the reflux of contents from the dorsal colon into the ventral colon.
Animals↗
Microscopic and functional anatomy of the ileal papilla and caecocolonic valve in the rat.
In the rat, topographic and X-ray studies of the caecum and ascending colon, together with microscopic anatomic observations of the ileal papilla and caecocolonic valve, showed that junction structures contribute to prevent the backflow of the caecal content into the ileum and to direct the ileal content within the caecum whatever the various positions of the caecum in the abdominal cavity.
Animals↗
Autoreactive T cells in normal mice: unrestricted recognition of self peptides on dendritic cell I-A molecules by CD4-CD8- T cell receptor alpha/beta+ T cell clones expressing V beta 8.1 gene segments.
CD4-CD8- double-negative (DN) and CD4+CD8- T cell clones were derived from splenic precursors resistant to killing by anti-Thy-1, -CD5, -CD4 and -CD8 monoclonal antibodies and complement. Both DN and CD4+ clones express functional T cell receptor (TcR) alpha/beta and exhibit strong autoreactivity in vitro. DN cells can be induced to proliferate by dendritic cells (DC) of all haplotypes tested, although this activation is inhibited by antibodies specific for I-A determinants expressed on the stimulatory DC. In contrast, CD4+ clones only respond to syngeneic or I-Ad-compatible DC. Both DN and CD4+ autoreactive clones do not proliferate when cultured with class II+ H-2d normal or tumor macrophages and B cell lines or with class II-transfected L cells, suggesting that these cells recognize self peptides only present on the surface of DC. Despite their phenotype resembling that of immature thymocytes and their inability to interact directly with B lymphocytes, DN cloned T cells, like CD4+ T cells, exhibit nonspecific helper functions and can induce polyclonal B cell proliferation and differentiation. DN TcR alpha/beta+ peripheral T cells represent, like TcR gamma/delta+ lymphocytes, a new T cell subset physiological role whose remains to be defined.
Animals↗
Polymorphism of Tcrb and Tcrg genes in Biozzi mice: segregation analysis of a new Tcrg haplotype with antibody responsiveness.
Tcrb and Tcrg gene polymorphism was investigated in high (H) and low (L) responder Biozzi mice from selection I, II, and GS by Southern blot analysis with appropriate V and C probes. No polymorphism of the Tcrb haplotype was detected between H and L mice in all selections which were all found to be of the BALB/c type. The H-I and H-II g genotype was of BALB/c and DBA/2 type, respectively. In contrast, a new Tcrg haplotype shared by L-I and L-II mice was identified and characterized by C gamma 1, 2, 3, C gamma 4, V gamma 1, 2, 3, V gamma 5, and V gamma 6 restriction fragment length polymorphisms (RFLPs). Tcrg genotypes were not fixed in the GS selection and two additional new haplotypes were identified in two L-GS mice. An attempt was made to correlate the L-I g genotype with the low responder status by analyzing g haplotypes among highest and lowest responder (H-I X L-I)F2 hybrids immunized with sheep red blood cells (SRBC). No correlation was found in this segregation study, whereas a highly significant one was established with the H-2 haplotype, a locus already known to participate in the genetic control of H-I/L-I difference. The lack of correlation between SRBC response and the Tcrg genotype was consistent with the heterogenous g haplotypes found in mice of the GS selection. Together, the present results suggest that H and L mice have the same Tcrab potential repertoire and that T-cell receptor (Tcr) genes cannot be considered as immune response genes in this model. Our results also indicate that the F2 segregation analysis, given a polymorphic gene, is suitable for an investigation of its immune response functions.
Animals↗
Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo-caeco-colonic junction.
The electromyogram of the terminal ileum, the caecum and the proximal right ventral colon was recorded in fasted conscious ponies receiving intravenously equiactive doses of pilocarpine (0.05 mg/kg) and carbachol (0.01 mg/kg) as acetylcholine analogues; cisapride (0.1 mg/kg) and metoclopramide (2 mg/kg) facilitating acetylcholine release from myenteric neurones and naloxone (0.05 mg/kg) as an antagonist of the endogenous inhibitory opioid system. Both cisapride and naloxone induced typical migrating spike bursts in the colon associated with contractions of caecal body and caecal base. Both pilocarpine and carbachol stimulated the terminal ileum but had opposite effects on the activity of the caeco-colonic segment which was decreased by pilocarpine and increased by carbachol. High doses of metoclopramide had weak and unspecific stimulatory motor effects. It is concluded that a true prokinetic effect at the equine ileo-caeco-colonic junction requires a motor profile which includes coordination between contractions sequentially involving the body and the base of the caecum and migrating spike bursts on the proximal colon. Such changes in the motor profile were produced by cisapride and naloxone and to a lesser extent by carbachol.
Animals↗
Pharmacological modulation of postprandial colonic motor activity in the pony.
The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but without inducing distinct patterns of activity. Atropine but not indomethacin or flunixin pre-treatment prevented the effects of postprandial, cholinergic and PGF2 alpha stimulation of colonic motility, suggesting that the gastrocolonic reflex involved mainly cholinergic stimulation of the caecum and replicated colon, including the prostaglandin F2 alpha excitatory effects.
Animals↗