Role of the thymus in the generation of skin-homing alpha beta and gamma delta virgin T cells.
Current models of lymphocyte traffic suggest that homing specificities of T cells to tissues such as skin are generated outside the thymus as a result of activation of naive T cells by antigen in lymph nodes. Virgin T cells are thought to home to high endothelial venules in lymph nodes, but are thought to be unable to home to extra-lymphoid tissues such as skin. We used the technique of in situ labeling of the thymus with fluorescein isothiocyanate to examine the homing specificities of authentically naive T cells in vivo, immediately after their export from the thymus. We report that homing specificities for skin as well as lymph node are imprinted on T cells inside the thymus, independent of antigen. We also show that both alpha beta and gamma delta emigrant T cells exhibit homing patterns to skin and lymph nodes which are identical to those of mature T cells. Our findings demonstrate a key role for the thymus in the induction of skin-homing specificities on T cells indicating that skin-homing specificities of T cells are not generated solely outside the thymus as a result of the activation of virgin T cells by antigen. The migration of thymic emigrants to extra-lymphoid tissues within a few hours of leaving the thymus may have implications for mechanisms of peripheral self-tolerance. This pathway provides an opportunity for direct virgin T cell interactions with self components only expressed in the periphery at a time when emigrants may be more susceptible to tolerance induction than mature circulating T cells.
Washington
E A
EA
Laboratory for Foetal and Neonatal Immunology, University of Melbourne, Parkville, Victoria 3052, Australia.
Kimpton
W G
WG
Holder
J E
JE
Cahill
R N
RN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D005434:Flow Cytometry; D019041:L-Selectin; D009928:Organ Specificity / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D012756:Sheep; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin