Differential effect of cholera toxin on CD45RA+ and CD45RO+ T cells: specific inhibition of cytokine production but not proliferation of human naive T cells.
We have studied how cholera toxin (CT) and its non-toxic cell-binding B-subunit (CTB) affect the activation of pure human T cells in an anti-CD3-driven system. CT, as opposed to CTB, strongly suppressed the proliferative responses as well as cytokine production in CD4+ and CD8+ T cells. CT however, had a differential effect on naive and activated/memory T cell subsets. Costimulation through exogenous IL-2 or through CD28 cross-linking rescued the proliferation of CT-treated naive CD45RA+ T cells, but not of activated/memory CD45RO+ cells. IL-2 production and IL-2 receptor expression were markedly reduced by CT in all T cell fractions, i.e. also in CD45RA+ cells which had maintained proliferative responses. However, the proliferative responses of CT-treated CD45RA+ T cells were IL-2-dependent, as shown by blocking experiments using anti-IL-2 antibodies. These results indicate (i) that CTB has no cytostatic effect on human T cells, (ii) that CT affects proliferation and cytokine production by two different signal pathways, and (iii) that CT might interact with a signal pathway generated through or influenced by CD45.
Department of Medical Microbiology and Immunology, Göteborg University, Göteborg, Sweden and INSERM 4 U 364, Nice, France. kristina.eriksson@microbio.gu.se
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Eriksson
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Nordström
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Czerkinsky
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Holmgren
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008222:Lymphokines / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D007376:Interleukin-2; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D016753:Interleukin-10; D005576:Colforsin; D015847:Interleukin-4; D007371:Interferon-gamma; D002772:Cholera Toxin; D000242:Cyclic AMP; D017493:Leukocyte Common Antigens