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Differential Responses of Invariant V24JQ T Cells and MHC Class II-Restricted CD4⁺ T Cells to Dexamethasone¹

Joshua D. Milner^2,3,*, Sally C. Kent^3,*, Timothy A. Ashley^*, S. Brian Wilson, Jack L. Strominger and David A. Hafler^4,*

^* Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, and Cancer Immunology and AIDS, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115

NK T cells are a T cell subset in the human that express an invariant -chain (V24^invt 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 V24^invt T cell clones and CD4⁺ T cell clones were investigated. Dexamethasone significantly enhanced anti-CD3-mediated proliferation of V24^invt T cells, whereas CD4⁺ T cells were inhibited. Addition of neutralizing IL-2 Ab partially abrogated dexamethasone-induced potentiation of V24^invt T cell proliferation, indicating a role for autocrine IL-2 production in corticosteroid-mediated proliferative augmentation. Dexamethasone treatment of anti-CD3-stimulated V24^invt T cells did not synergize with anti-Fas blockade in enhancing proliferation or preventing AICD. The V24^invt 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 V24^invt T cells and CD4⁺ T cells; at higher doses of anti-CD3, which caused inhibition of CD4⁺ T cells, the V24^invt T cell clones proliferated and were rescued from AICD. These results demonstrate significant differences in TCR signal strength required between V24^invt T cells and CD4⁺ cells, and suggest important immunomodulatory consequences for endogenous and exogenous corticosteroids in immune responses.

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