Stimulation via the CD3 and CD28 molecules induces responsiveness to IL-4 in CD4+CD29+CD45R- memory T lymphocytes.
Although both IL-2 and IL-4 can promote the growth of activated T cells, IL-4 appears to selectively promote the growth of those helper/inducer and cytolytic T cells which have been activated via their CD3/TCR complex. The present study examines the participation of CD28 and certain other T cell-surface molecules in inducing T cell responsiveness to IL-4. Purified small high density T cells were cultured in the absence of accessory cells with various soluble anti-human T cell mAb with or without soluble anti-CD3 mAb and their responsiveness to IL-4 was studied. None of the soluble anti-T cell mAb alone was able to induce T cell proliferation in response to IL-4. A combination of soluble anti-CD3 with anti-CD28 mAb but not with mAb directed at the CD2, CD5, CD7, CD11a/CD18, or class I MHC molecules induced T cell proliferation in response to IL-4. Anti-CD2 and anti-CD5 mAb enhanced and anti-CD18 mAb inhibited this anti-CD3 + anti-CD28 mAb-induced T cell response to IL-4. In addition, anti-CD2 in combination with anti-CD3 and anti-CD28 mAb induced modest levels of T cell proliferation even in the absence of exogenous cytokines. IL-1, IL-6, and TNF were each unable to replace either anti-CD3 or anti-CD28 mAb in the induction of T cell responsiveness to IL-4, but both IL-1 and TNF enhanced this response. The anti-CD3 + anti-CD28 mAb-induced response to IL-4 was exhibited only by cells within the CD4+CD29+CD45R- memory T subpopulation, and not by CD8+ or CD4+CD45R+ naive T cells. When individually cross-linked with goat anti-mouse IgG antibody immobilized on plastic surface, only anti-CD3 and anti-CD28 mAb were able to induce T cell proliferation. These results indicate that the CD3 and CD28 molecules play a crucial role in inducing T cell responsiveness to IL-4 and that the CD2, CD5, and CD11a/CD18 molecules influence this process.
Damle
N K
NK
Department of Immunology, CETUS Corporation, Emeryville, CA 94608.
Doyle
L V
LV
D000276:Adjuvants, Immunologic / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000502:physiology; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D003432:Cross-Linking Reagents; D006801:Humans; D007156:Immunologic Memory; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D017493:Leukocyte Common Antigens