In vivo treatment of class II MHC-deficient mice with anti-TCR antibody restores the generation of circulating CD4 T cells and optimal architecture of thymic medulla.
TCR ligation by the self-peptide-associated MHC molecules is essential for T cell development in the thymus, so that class II MHC-deficient mice do not generate CD4(+)CD8(-) T cells. The present results show that the administration of anti-TCR mAb into class II MHC-deficient mice restores the generation of CD4(+)CD8(-) T cells in vivo. The CD4 T cells were recovered in the thymus, peripheral blood, and the spleen, indicating that the anti-TCR treatment is sufficient for peripheral supply of newly generated CD4 T cells. Unlike peripheral CD4 T cells that disappeared within 5 wk after the treatment, CD4(+)CD8(-) thymocytes remained undiminished even after 5 wk, suggesting that CD4 T cells in the thymus are maintained separately from circulating CD4 T cells and even without class II MHC molecules. It was also found that the mass of medullary region in the thymus, which was reduced in class II MHC-deficient mice, was restored by the anti-TCR administration, suggesting that the medulla for CD4(+)CD8(-) thymocytes is formed independently of the medulla for CD4(-)CD8(+) thymocytes. These results indicate that in vivo anti-TCR treatment in class II MHC-deficient mice restores the generation of circulating CD4 T cells and optimal formation of the medulla in the thymus, suggesting that anti-TCR Ab may be useful for clinical treatment of class II MHC deficiencies.
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015704:CD4 Antigens / Q000096:biosynthesis / Q000097:blood; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000097:blood / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D005333:Fetus; D019674:Genes, T-Cell Receptor beta / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006825:Hybridomas; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II