Abstract
NK T cells are a T cell subset in the human that express an invariant alpha-chain (V alpha 24invt T cells). Because of the well-described immunomodulation by glucocorticoids on activation-induced cell death (AICD), the effects of dexamethasone and anti-CD3 stimulation on V alpha 24invt T cell clones and CD4+ T cell clones were investigated. Dexamethasone significantly enhanced anti-CD3-mediated proliferation of V alpha 24invt T cells, whereas CD4+ T cells were inhibited. Addition of neutralizing IL-2 Ab partially abrogated dexamethasone-induced potentiation of V alpha 24invt T cell proliferation, indicating a role for autocrine IL-2 production in corticosteroid-mediated proliferative augmentation. Dexamethasone treatment of anti-CD3-stimulated V alpha 24invt T cells did not synergize with anti-Fas blockade in enhancing proliferation or preventing AICD. The V alpha 24invt T cell response to dexamethasone was dependent on the TCR signal strength. In the presence of dexamethasone, lower doses of anti-CD3 inhibited proliferation of V alpha 24invt T cells and CD4+ T cells; at higher doses of anti-CD3, which caused inhibition of CD4+ T cells, the V alpha 24invt T cell clones proliferated and were rescued from AICD. These results demonstrate significant differences in TCR signal strength required between V alpha 24invt T cells and CD4+ cells, and suggest important immunomodulatory consequences for endogenous and exogenous corticosteroids in immune responses.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Antibodies, Blocking / pharmacology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD1 / immunology
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Antigens, CD1d
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Antigens, Differentiation, B-Lymphocyte / metabolism*
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Apoptosis / drug effects
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Apoptosis / immunology
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Autocrine Communication / drug effects
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Autocrine Communication / immunology
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CD3 Complex / immunology
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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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Clone Cells
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Dexamethasone / pharmacology*
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Dose-Response Relationship, Immunologic
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Histocompatibility Antigens Class II / immunology*
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Histocompatibility Antigens Class II / metabolism*
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Humans
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Immunosuppressive Agents / pharmacology
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Interleukin-2 / metabolism
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Receptors, Antigen, T-Cell, alpha-beta / immunology*
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Signal Transduction / drug effects
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Signal Transduction / immunology
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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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fas Receptor / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Blocking
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Antibodies, Monoclonal
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Antigens, CD1
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Antigens, CD1d
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Antigens, Differentiation, B-Lymphocyte
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CD1D protein, human
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CD3 Complex
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Histocompatibility Antigens Class II
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Immunosuppressive Agents
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Interleukin-2
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Receptors, Antigen, T-Cell, alpha-beta
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fas Receptor
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invariant chain
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Dexamethasone