A role for the mevalonate pathway in the induction of subtype cross-reactive immunity to influenza A virus by human gammadelta T lymphocytes
Center for Infectious Disease and Vaccine Research; Division of Infectious Diseases and Immunology, Department of Medicine
The major gammadelta T cell subset in the human peripheral blood expresses the Vgamma9delta2 TCR and recognizes non-peptidic prenyl pyrophosphate antigens such as isopentylpyrophosphate (IPP). Upon activation the gammadelta T cells rapidly secrete antiviral cytokines similar to classical memory alphabeta T cells. Here we have investigated the ability of gammadelta T lymphocytes from human PBMC to become activated by influenza A virus infection. Vgamma9Vdelta2 T lymphocytes rapidly upregulate expression of CD25 and CD69 and produce IFN-gamma following influenza infection of PBMC. Moreover, the recognition is cross-reactive between various subtypes of influenza, but not with vaccinia virus. Vgamma9Vdelta2 T cell responses are potently reduced by the HMG-CoA reductase inhibitor mevastatin, which inhibits the mevalonate pathway and IPP synthesis. Our results indicate that influenza virus infection induces the rapid activation and function of Vgamma9Vdelta2 T lymphocytes in the peripheral blood via a mechanism that depends on the mevalonate pathway.
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Citation: Cell Immunol. 2010;264(1):71-7. doi: 10.1016/j.cellimm.2010.04.013. Epub 2010 May 4. Link to article on publisher's site
Jameson, Julie M.; Cruz, John; Costanzo, Anne; Terajima, Masanori; and Ennis, Francis A., "A role for the mevalonate pathway in the induction of subtype cross-reactive immunity to influenza A virus by human gammadelta T lymphocytes" (2010). Infectious Diseases and Immunology Publications and Presentations. 242.