Cellular interplay among Th17, Th1, and Treg cells in HIV‐1 subtype “C” infection

Abstract

CD4 T cell depletion is central to HIV pathogenesis and disease progression. Different subsets of CD4 T cells cooperate to combat an infection. Therefore, the immune balance among Th17, Th1, and Treg cells may be critical in HIV immunopathogenesis which is not adequately defined yet. The impact of HIV-1 infection on the interplay of Th17/Th1/Treg cells in HIV-1 infected Indian individuals was examined in the present study and report that HIV-1 Gag specific peripheral blood Th17 cells were significantly depleted in late infected subjects, compared to early infected subjects and slow progressors. Although, the gradual loss of Th1 cells was also reported during HIV-1 disease progression but relative to Th17 cells, Th1 cells were found to be more resistant to HIV-1 infection. Additionally, a significant and progressive gain in Treg cellular frequency was observed as disease progress from early to late stage of HIV-1 infection. This study also indicate that slow progressors might have an intrinsic capacity to develop strong HIV-1 specific Th17 and Th1 cell responses contrasted with a faint Treg cellular performance signifies the importance of these cellular subsets in progressive versus nonprogressive HIV-1 infection. A significant gradual loss of Th17/Treg ratio was found to be associated with disease state, plasma viral load and immune activation.

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

“…As this last T-cell subset is known to suppress T-cell responses, negative correlations with levels of immune activation could be expected, however we found direct correlations with CD8 + T-cell activation and VL, and an inverse relationship with CD4 counts. These results are in line with recent studies which described direct correlations between Treg cells and T-cell activation 22 or disease progression 23 , and inverse correlations with CD4 frequencies 22 , thus supporting the hypothesis of a detrimental role for this subset or the expansion of non-functional Tregs during HIV infection.…”

“…Within the PHI cohort, we found a trend towards a Th17 reduction between baseline and one year p.i samples, however significant differences were not reached in line with previous studies 13 23 . However, at baseline we found a clear difference between RPs and TPs in relation to CD8 + T-cell activation, VL and Th17 counts.…”

Acquired immunodeficiencies and tuberculosis: focus on HIV/AIDS and diabetes mellitus

“…In animals Treg depletion during Mtb infection reduced pathology and bacterial burden, while the reverse was seen following adoptive transfer of Tregs (63,64), suggesting that these cells contribute significantly to the regulation of bacterial containment in vivo. Acquired immunodeficiencies due to HIV or impaired immunity due to T2DM may alter the balance between effector and regulatory T cells (65)(66)(67)(68)(69)(70).…”

7-oxo-DHEA enhances impaired M. tuberculosis-specific T cell responses during HIV-TB coinfection

“…We observed that Mtb stimulation increased the numbers of lymphocytes with a regulatory phenotype over Th1 CD4 + T cells (lower Th1/FoxP3, Th1/Tregs, Th1/uTregs and Th1/FoxP3 + T-bet+ ratios in patients). Other authors suggested that it would be useful for monitoring progression of infection to focus on the study of the relative balance between Th1/regulatory cells rather than on the analysis of a specific cell subset [55]. We discovered 7-OD and DHEA augmented Th1/uTregs ratio, but only 7-OD could reverse the effect of Mtb in terms of the balance of Th1/FoxP3, Th1/Tregs and Th1/FoxP3 + T-bet+ in HIV-TB individuals.…”