Human CD4+CD45R0+ and CD4+CD45RA+ T cells synergize in response to alloantigens.
Alloantigens, unlike recall antigens, activate both CD45RA+ (naive) and CD45R0+ (memory) CD4+ cells to the same extent. These T cell subsets may therefore interact with each other in response to alloantigens on transplanted grafts. We have investigated if the ability of activated CD4+CD45RA+ and CD4+CD45R0+ T cells to produce and respond to interleukin 2 (IL2) and IL4 may be involved in this interaction. After activation, both subsets up-regulate their IL2 receptor (IL2R) and IL4R expression, yet IL4 substantially enhanced the proliferation of the CD4+CD45RA+ but not of the CD4+CD45R0+ T cell subset, while IL2 increased the proliferation of CD4+CD45R0+ but not of the CD4+CD45RA+ T cells. Significantly, the CD4+CD45RA+ T cells synthesized two- to threefold more mRNA for IL2 than the CD4+CD45R0+ subset, while the CD4+CD45R0+ T cells synthesized mRNA for IL4 and interferon-gamma exclusively. The addition of IL2 to alloactivated CD4+CD45R0+ T cells further up-regulated their production of all three lymphokine mRNA; in contrast, IL4 induced an increase in mRNA for IL2 in only the alloactivated CD4+CD45RA+ subset. The reciprocity in the ability of both these CD4+ T cells to synthesize and respond to IL2 and IL4 may provide a rationale for the regulation of lymphokine interactions in vivo. Furthermore, the synergy between these subsets in response to alloantigens, which was directly quantitated by co-culturing CD4+CD45RA+ and CD4+CD45R0+ cells together prior to activation, may potentiate the alloreactivity against transplanted grafts in vivo.
Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, GB.
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Akbar
M
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Salmon
K
K
Ivory
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S
Taki
D
D
Pilling
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G
Janossy
D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens