Immune signatures for HIV-1 and HIV-2 induced CD4⁺T cell dysregulation in an Indian cohort.

ABSTRACT:

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 CD4⁺T 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 CD4⁺T cell subsets, expressing CD25 (IL-2R?) 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 CD4⁺T and CD8⁺T 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 CD4⁺T 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-2R? and IL-7R?. 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 CD4⁺T 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 CD4⁺T and CD8⁺T cells in chronic HIV-2 infection. Lower immune activation in these individuals indicates that persistent immune activation driven CD4⁺T 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.

SUBMITTER: Salwe S 

PROVIDER: S-EPMC6371624 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature