Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone.
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.
Milner
J D
JD
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kent
S C
SC
Ashley
T A
TA
Wilson
S B
SB
Strominger
J L
JL
Hafler
D A
DA
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018949:Antigens, CD1 / Q000276:immunology; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D019898:Autocrine Communication / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D003907:Dexamethasone / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000944:Antigens, Differentiation, B-Lymphocyte; C526877:CD1D protein, human; D017252:CD3 Complex; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; C045084:invariant chain; D003907:Dexamethasone