Circulating Vdelta2 T lymphocytes are involved in the response to mycobacteria and certain viruses, while Vdelta1 T cells, resident in the mucosal tissues, participate in the immunity against intracellular microrganisms. Vdelta2 T cells recognize non-peptidic phosphorylated antigens expressed by mycobacteria, whereas Vdelta1 T cells interact with MHC-related molecules (MICA, MICB) and with receptors for the UL-16 protein produced by CMV-infected cells. Vdelta1 T cells release IFNgamma upon challenge with MICA+ cells, while Vdelta2 T cells secrete this cytokine upon stimulation with phosphate antigens. We reported that in early HIV-1 infection Vdelta1 T lymphocytes, producing IFNgamma, are increased in the peripheral blood. We addressed the question of whether this T cell subset can also be involved in the response to fungal infections.
Thirty untreated HIV-1-infected patients were studied, compared to ten healthy subjects. Patients were staged according to the Center for Disease Control criteria. Serum HIV-1 RNA was quantitated and CD4 count performed. Cytokine production was determined by intracytoplasmic immunofluorescence and ELISA. Proliferation of Vdelta1 and Vdelta2 T cells to C. albicans, PPD, CMV and P. Carinii was determined by flow cytometry after CFSE staining. Gene expression was evaluated by Q-RT-PCR.
We show that: 1) a population of circulating Vdelta1 T lymphocyte producing both IFN-gamma and IL-17 is expanded in HIV-1 infected patients; 2) this population is capable of proliferating and enhancing cytokine production in response to Candida albicans, while Vdelta2 T cells respond to mycobacterial antigens; 3) IFN-gamma/IL-17 double producers express the RORC and the TXB21 transcription factors, the CCR7 homing receptor, the CD161 molecule involved in transendothelial migration, and the CCR4 and CCR6 chemokine receptors.
In HIV-1 patients, gammadelta T cells not only produce Th1/Th17 cytokines, but express a number of homing and chemokine receptors, thus being equipped for recirculation through lymph nodes and peripheral tissues. This circulating memory gammadelta T cell subset might play an important role in the control of HIV-1 spreading and in the defence against opportunistic infections, possibly contributing to compensate the impairment of CD4+ T cells.