Abstract
Alteration of γδ T-cell distribution and function in peripheral blood is among the earliest defects during HIV-infection. We asked whether the polyfunctional response could also be affected, and how this impairment could be associated to CD4 T-cell count. To this aim, we performed a cross-sectional study on HIV-infected individuals. In order to evaluate the polyfunctional-Vγ9Vδ2 T-cell response after phosphoantigen-stimulation, we assessed the cytokine/chemokine production and cytotoxicity by flow-cytometry in HAART-treated-HIV+ persons and healthy-donors. During HIV-infection Vγ9Vδ2-polyfunctional response quality is affected, since several Vγ9Vδ2 T-cell subsets resulted significantly lower in HIV+ patients in respect to healthy donors. Interestingly, we found a weak positive correlation between Vγ9Vδ2 T-cell-response and CD4 T-cell counts. By dividing the HIV+ patients according to CD4 T-cell count, we found that Low-CD4 patients expressed a lower number of two Vγ9Vδ2 T-cell subsets expressing MIP-1β in different combinations with other molecules (CD107a/IFNγ) in respect to High-CD4 individuals. Our results show that the Vγ9Vδ2 T-cell-response quality in Low-CD4 patients is specifically affected, suggesting a direct link between innate Vγ9Vδ2 T-cells and CD4 T-cell count. These findings suggest that Vγ9Vδ2 T-cell quality may be indirectly influenced by HAART therapy and could be included in a new therapeutical strategy which would perform an important role in fighting HIV infection.
Highlights
Human γδ T-cells are critical components of the innate immune system and play important roles in the early response to invading pathogens
PBMC from the HD and HIV+ subjects were stimulated with Picostim, and the ability of Vγ9Vδ2 T-cells to produce cytokines and chemokines and to exert cytotoxicity were analyzed by flow cytometry
HIV infection causes an alteration of γδ T-cell distribution leading to a specific depletion of Vγ9Vδ2 T-cells in peripheral blood [3,10]
Summary
Human γδ T-cells are critical components of the innate immune system and play important roles in the early response to invading pathogens. Vγ9Vδ2 T-lymphocytes, the major population among γδ T-cells, display beneficial roles, as they are able to control HIV infection [1] and exhibit antiviral potential through their cell-lytic function and cytokine/chemokine secretions [2]. 10, 2015 γδ T Cell Responses in HIV Infection γδ T-cells have been found to generally decrease with the advancement of HIV infection [4], the antiviral functions of Vγ9Vδ2 T-cells can be enhanced by stimulation with phosphoantigen [5], suggesting a novel target for therapeutic strategies. It was demonstrated that polyfunctional αβ T-cells are strongly associated with natural control of HIV disease, being higher in HIV-infected persons who spontaneously control the virus without any treatment regimen The ability of HAART treatment to restore polyfunctionality in T-cells is still controversial [7,8]
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