Objective. To investigate the role of $6 T cells in Mycobacterium tuberculosk-induced rat adjuvant arthritis.Methods. Rats with adjuvant arthritis were injected With the anti-T cell receptor $6 (anti-TCRy'S) monoclonal antibody V65 according to a preventive protocol, a pre-arthritis peak protocol, and a late therapeutic protocol. Arthritis severity and joint destruction were monitored, and depletion of target cells was analyzed by flow cytometry.Results. Although all protocols led to successful depletion of TCRy'$''@" cells in peripheral blood and lymph nodes, none of the regimens influenced clinical parameters of adjuvant arthritis. If rats were treated before the clinical peak of adjuvant arthritis, however, joint destruction was significantly more severe than in vehicle-treated rats.Conclusion. Rat adjuvant arthritis is not promoted or perpetuated by y'S T cells. Aggravation of joint destruction with pre-arthritis peak anti-$6 treatment suggests a stage-dependent protective role of y's T cells in adjuvant arthritis.-~ Ms Pelegri

Two monoclonal antibodies with specificity for rat gammadelta T cell receptor (TCR) were generated. One, called V65, reacts with all CD3+ alphabeta TCR- rat Tcells and thus recognizes a constant determinant of the rat gammadelta TCR (Kühnlein et al., Journal of Immunology 1994, 153: 979). The other, called V45, reacts with approximately 80% of gammadelta T cells in peripheral lymphoid organs. In rat epidermis, V65 but not V45 detects a dense network of the dendritic epidermal Tcells (DETC). Analysis of epidermal RNA by polymerase chain reaction (PCR) indicated that Vgamma3 and Vdelta1 are the predominant, if not exclusive TCR V transcripts present at this site. Sequence analysis of cDNA clones obtained by reverse transcription-PCR with Vgamma3- and Vdelta1-specific primers revealed that the variable domains of rat DETC gamma and delta chains are very homologous to those described in mice (92% and 95% identity at the protein level). The complete conservation between the two species of the amino acid sequences at the V-(D)-J transitions of this monomorphic receptor indicates that the interaction of the DETC TCR with its as yet unknown ligand must be of central importance for DETC function.

In the present study, we have analyzed the appearance and maturation of γ/δ T cells, recognized with a new mAb V65, in the central and peripheral lymphoid organs of fetal, neonatal, and adult Wistar rats. Cytofluorometrical analysis demonstrated the first V65+ γ/δ T cells in the thymus of 16-17-day embryonic rats, although by immunohistology, they were identified only in 19-day rat embryos in both the cortico-medullary border and thymic medulla. Phenotypically, γ/δ thymocytes from fetal and neonatal thymus expressed CD3, CD2, and CD5, but only 60-80% were CD8+ and approximately 40-50% expressed the α chain (p55) of the IL-2R. In the periphery, the immunohistological study identified for the first time ,γ/δ T cells in the splenic white pulp and the gut of 21-day fetal rats, where they occurred within the epithelium as well as in the lamina propria. After birth, γ/δ lymphocytes appeared in the skin, where they were present as dendritic epidermal T cells in increasing numbers during postnatal life. Whereas these γ/δ T cells formed the predominant T-cell population in the rat skin, γ/δ T cells in peripheral lymphoid organs, BALT, or the gut only represented a minor T-cell population. These results are discussed in comparison to γ/δ T cells of other vertebrate species.

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The biologic role and repertoire of cells bearing the gamma delta T cell receptor has not been fully defined. However, their tropism for epithelial microenvironments is recognized and suggests an important role for these cells in immune defense at mucosal tissue surfaces. The study presented below utilizes an experimental model in which repeated exposure of Brown Norway rats to OVA by inhalation induces a state of Ag-specific, IgE isotype-specific "tolerance" via immune deviation. This process seems similar to oral tolerance in the gut. This form of tolerance was adoptively transferred to naive syngeneic recipients by i.p. injection of as few as 10(3) positively selected TCR-gamma delta+ cells from OVA-exposed rats. These TCR-gamma delta+ T-cells are demonstrated to produce high levels of INF-gamma in response to OVA stimulation, and this provides a potential mechanism for the inhibition of Th2 cell proliferation, resulting in suppression of IgE production. The unique potency of these cells in selective suppression of IgE Ab production in response to natural "mucosal" Ag exposure suggests a potentially important role in protection against primary allergic sensitization in vivo.