Early development of the T cell repertoire. In vivo treatment of neonatal mice with anti-Ia antibodies interferes with differentiation of I-restricted T cells but not K/D-restricted T cells.
Monoclonal antibodies to I-Ak were injected into neonatal H-2k mice for a period of 3 wk. The spleens of such mice are devoid of Ia-positive cells. Allo- and trinitrophenyl (TNP)-self-specific cytotoxic T lymphocyte (CTL) responses in such anti-I-A-treated mice were almost completely abrogated at the end of the 2-3 wk in vivo treatment period. Development of suppressor cells, carry-over of blocking antibodies, lack of responder accessory cells, or defective CTL function were not responsible for the observed defect. As concanavalin A supernatant could restore the defect, it is more likely that the defect is due to the absence of competent Ia-specific T helper cells. In addition, anti-I-A-treated mice exhibit reduced I-A antigen expression in the thymus and defective Ia-bearing accessory cell function in the spleen. It is postulated that, for development of Ia-specific T cells to occur, precursor T cells need to interact with Ia-encoded products in the thymus, and anti-Ia treatment interferes with this process. Finally, the mechanism of this interference was shown to be due to actual removal or functional inactivation of those I-A-positive elements responsible for the education of I-A-recognizing T cells, since in (H-2b X H-2k)F1 mice, treatment with anti-I-Ak antibodies results in abrogation of CTL responses to TNP in association with both parental haplotypes, while in the thymus of these mice expression of both I-Ak and I-Ab was reduced.
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II