Activation and ‘deletion’ of self-reactive mature and immature T cells during ontogeny of Mls-1a mice: implications for neonatal tolerance induction

Publisher Website
Google Scholar
Abstract
We assessed the kinetics of Vβ6+ T cell elimination in the lymph nodes and thymus during Mls-1a mouse ontogeny. Our results suggest that induction of tolerance to Mls-1a antigens involves mechanisms other than clonal deletion of immature T cells in the thymus. Mature CD4+CD8− (CD4SP) T cells were affected by Mls-1a antigens earlier than immature thymocyte populations. Up to 2 weeks after birth, reduced frequencies of Vβ6+ T cells were detected only in CD4SP cells from the thymus and lymph nodes, and generation of CD4SP cells in the thymus was blocked at least 1 week earlier than that of their CD4+CD8loTCRhl immature precursors. The number of Vβ6+CD4SP T cells increased during the first 2 weeks of life and remained constant thereafter. We thus found no evidence of deletion of mature Vβ6+CD4SP T cells, as the reduced frequencies in adult mice can be attributed to the dilution of previously generated cells in lymphoid organs of growing mice, which increase in cellulartty after birth. Vβ6+CD4+ T cells were activated in vivo shortly after birth, as shown by a selective increase in IL-2 receptor a chain expression in the thymus and lymph nodes from day 0 to day 2 after birth. It is therefore likely that endogenous expression of Mls-1a antigen shortly after birth activates Vβ6+CD4SP T cells and renders them anergic. This process of tolerance induction may precede the clonal deletion of immature T cells in the thymus, described in the adult mouse.

This publication has 0 references indexed in Scilit: