Deficient CD4+ T cell proliferation in the class 1 MHC-restricted 2C TCR-transgenic mouse.
A comparative study of immune function and marker expression of CD4+ T cells from MHC class 1-restricted 2C TCR-transgenic (2C+) and control transgene-negative littermate (2C-) mice was performed. While 2C+CD4+ T cells resembled memory T cells on the basis of CD44highCD45RBlow expression, the majority of 2C-CD4+ T cells were of the CD44lowCD45RBhigh naive phenotype. Slightly lower levels of TCR-beta and CD3 were found on 2C+CD4+ T cell than 2C-CD4+ T cells. Vigorous proliferation by 2C-CD4+ T cells was observed upon stimulation with 1) anti-CD3 mAb presented through the FcR of macrophages; 2) immobilized (plate-bound) anti-CD3 + anti-CD28 mAbs; and 3) PMA + ionomycin. In marked contrast, all three mitogenic stimuli stimulated highly deficient proliferative responses by 2C+CD4+ T cells. However, significant IL-2 production was detected both in anti-CD3 and in PMA + ionomycin-stimulated cultures of 2C+CD4+ T cells. While intracellular calcium in 2C-CD4+ T cells rapidly increased following anti-CD3 addition, no such increase was observed for similarly stimulated 2C+CD4+ T cells. Anti-CD28, PMA, and coculture with 2C-CD4+ T cells each failed to significantly correct the deficient 2C+CD4+ T cells proliferation as induced by anti-CD3. In addition, IL-2, IL-4, and IL-7 supplements also failed to reverse the deficient proliferation of 2C+CD4+ T cells despite expression of IL-2R component alpha-, beta-chains and the gamma-chain common also to IL-4R and IL-7R. Thymus CD4+8- T cells from the 2C-transgenic mouse were similarly deficient in proliferation as spleen CD4+ T cells. A small subpopulation of CD4+ T cell from the 2C-transgenic mouse expressed the transgenic TCR alpha:beta heterodimer as detected by the 1B2 anti-2C clonotypic mAb; both 1B2+ and 1B2- subpopulations proliferated poorly in response to anti-CD3 and to PMA + ionomycin. These results raise the possibility that TCR engagement with MHC class 1 molecules during early intrathymic development can result in the emergence of CD4+ T cells characterized by unusual marker expression and function.
Chen
F L
FL
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Kung
J T
JT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics*; D007164:Immunosorbents; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008231:Lymphopenia / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D006183:H-2 Antigens; D007164:Immunosorbents; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate