Anti-CD11a prevents deletion of self-reactive T cells in neonatal C57BR mice.
The process of thymic maturation permits development of T cells expressing receptors which recognize self-major histocompatibility complex (MHC) determinants, but deletes T cells recognizing self-MHC determinants with high affinity. This selection process is evolutionarily conserved, and presumably serves in part to prevent the release of autoreactive cells. However, the mechanisms involved in the selection process, and the molecules required are incompletely characterized. Lymphocyte function-associated antigen-1 (LFA-1) is an accessory molecule important in T-cell activation, is involved in thymocyte-epithelial cell binding, and contributes to the maturation of CD4-CD8- thymocytes to the CD4+CD8+ stage. In this report we have investigated whether LFA-1 also contributes to the thymic deletion of potentially self-reactive cells. Neonatal C57Br mice were injected with amounts of a monoclonal antibody to LFA-1 that saturated thymic binding sites, then splenocytes were examined for T cells expressing receptors normally deleted in the thymus. The results demonstrate that V beta 17a+ T cells, normally deleted in this strain, can be detected in the spleen following administration of anti-LFA-1, thus supporting the hypothesis that LFA-1 also contributes to negative selection. The potential significance of LFA-1 involvement in multiple thymic maturation events is discussed.
Quddus
J
J
Department of Medicine, University of Michigan, Ann Arbor.
Kaplan
A
A
Richardson
B C
BC
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D018845:CD11 Antigens / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D017634:Self Tolerance / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016693:Receptors, Antigen, T-Cell, alpha-beta