Immune signatures for HIV-1 and HIV-2 induced CD4T cell dysregulation in an Indian cohort.

BACKGROUND

HIV-2 infection is characterised by a longer asymptomatic phase and slower AIDS progression than HIV-1 infection. Identifying unique immune signatures associated with HIV-2 pathogenesis may thus provide therapeutically useful insight into the management of HIV infection. This study examined the dynamics of the CD4T cell compartment, critical in disease progression, focussing on chronic HIV-2 and HIV-1 infected individuals at various stages of disease progression.

METHODS

A total of 111 participants including untreated and treated HIV infected individuals and seronegative individuals were enrolled in this study. The relative proportion of CD4T cell subsets, expressing CD25 (IL-2Rα) and CD127 (IL-7R), in HIV infected individuals and seronegative controls were assessed by multiparametric flow cytometry. Additionally, levels of immune activation and cytotoxic T lymphocytes in both the CD4T and CD8T cell compartments was evaluated.

RESULTS

Both treated and untreated, HIV-1 and HIV-2 infected individuals showed apparent dysregulation in CD4 T cell subset frequency that was associated with disease progression. Furthermore, longitudinal sampling from a group of HIV-1 infected individuals on virologically effective ART showed no significant change in dysregulated CD4T cell subset frequency. For both ART naïve and receiving groups associations with disease progression were strongest and significant with CD4 T cell subset frequency compared to per cell expression of IL-2Rα and IL-7Rα. In untreated HIV-2 infected individuals, T cell activation was lower compared to ART naïve HIV-1 infected individuals and higher than seronegative individuals. Also, the level of Granzyme-B expressing circulating T cells was higher in both ART-naïve HIV-1 and HIV-2 infected individuals compared to seronegative controls.

CONCLUSION

Dysregulation of IL-2 and IL-7 homeostasis persists in CD4T cell subsets irrespective of presence or absence of viremia or antiretroviral therapy in HIV infection. Furthermore, we report for the first time on levels of circulating Granzyme-B expressing CD4T and CD8T cells in chronic HIV-2 infection. Lower immune activation in these individuals indicates that persistent immune activation driven CD4T cell depletion, as observed in untreated HIV-1 infected individuals, may not be as severe and provides evidence for a disparate pathogenesis mechanism. Our work also supports novel immunomodulatory therapeutic strategies for both HIV-1 and HIV-2 infection.