Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Division / drug effects
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Cholera Toxin / pharmacology*
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Colforsin / pharmacology
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Cyclic AMP / physiology
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Humans
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Interleukin-2 / analysis
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Interleukin-4 / metabolism
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Leukocyte Common Antigens / analysis*
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Leukocyte Common Antigens / physiology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / physiology*
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Lymphokines / metabolism*
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Receptors, Antigen, T-Cell / immunology
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Recombinant Proteins / pharmacology
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Second Messenger Systems
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Signal Transduction / physiology
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T-Lymphocyte Subsets / drug effects*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Th1 Cells / drug effects
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / drug effects
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Interleukin-2
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Lymphokines
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Receptors, Antigen, T-Cell
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Recombinant Proteins
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Interleukin-10
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Colforsin
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Interleukin-4
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Interferon-gamma
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Cholera Toxin
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Cyclic AMP
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Leukocyte Common Antigens