Differential effects of CD4 and CD8 engagement on the development of cytokine profiles of murine CD4+ and CD8+ T lymphocytes.
A simple culture system devoid of antigen-presenting cells was used to examine the ability of immobilized antibodies to lymphocyte function-associated antigen-1 (LFA-1) (CD11a), CD28 and CD4 or CD8 to modulate the responses of normal murine CD4+ and CD8+ lymph node T cells to immobilized anti-CD3 antibody and interleukin-2 (IL-2). All the antibodies enhanced proliferative responses to limiting anti-CD3 antibody. Both CD4+ and CD8+ cells produced substantial titres of IL-3 and interferon-gamma (IFN-gamma) in primary and secondary cultures regardless of the coactivating antibodies used for priming. By contrast, the combination of anti-CD4 with anti-CD3 antibody stimulated significantly higher titres of IL-4 than any other antibody combination in cultures of CD4+ cells. This CD4-dependent IL-4 response was induced in CD4+ T cells of naive (CD44low) phenotype and was similar in magnitude to the response induced by exogenous IL-4 but, unlike the latter, was not associated with elevated IL-3 synthesis. A comparable effect of anti-CD8 antibodies on CD8+ cells was not observed: although IL-4 production by CD8+ cells was induced by exogenous IL-4, it was not detected following coactivation with anti-CD8 or any other antibodies. We conclude that anti-CD4 antibody is a potent inducer of IL-4-secreting CD4+ T cells whose effects can be distinguished from those of anti-CD8 antibody on CD8+ T cells and from those of IL-4 on either subset.
Campbell
S B
SB
The Queensland Institute of Medical Research and the Joint Transplantation Biology Program, The University of Queensland, Brisbane, Queensland, Australia.
Komata
T
T
Kelso
A
A
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma; D007377:Interleukin-3 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007377:Interleukin-3; D016169:Lymphocyte Function-Associated Antigen-1; D015847:Interleukin-4; D007371:Interferon-gamma