P13. iNKT and NK activation in HIV-1 and HIV-2 infections associate with CD4 level and viral load.

David FG Malone¹*, Susanna M Bächle¹*, Marcus Buggert², Antonio Biague³, Hans Norrgren⁴, Patrik Medstrand⁵, Markus Moll¹, Johan K Sandberg¹, Marianne Jansson⁶, SWEGUB CORE group

Affiliates: ¹Centre for Infectious Medicine, Department of Medicine Huddinge, ²Department of Laboratory Medicine, ²Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Sweden ³National Public Health Laboratory, Bissau, Guinea-Bissau ⁴Department of Clinical Sciences, ⁵Department of Laboratory Medicine Malmö, ⁶Department of Laboratory Medicine Lund, Lund University, Sweden *Authors contributed equally

Background
HIV-1, being present globally, has had its interactions with the immune system studied extensively, relative to the less common HIV-2 that exhibits reduced aggressiveness and transmissibility. This cross-sectional analysis assessed the activation of the innate lymphocytes iNKT and NK cells in HIV-1, HIV-2 and dually HIV-1/HIV-2 (HIV-D) infected individuals, as well as HIV negative controls.

Methods
From a prospectively followed cohort residing in Guinea-Bissau, we received whole blood samples from participants whom were treatment naive. Multi-colour flow cytometry was conducted for the analysis of iNKT and NK subsets and results were related to HIV status, % CD4+ T cells and viral load.

Results
Significant reductions in numbers of iNKT cells were observed in HIV-1 associated infections, while HIV-2 viremic individuals had fewer CD4+ iNKT cells. CD56dim NK cell counts tended to be lower in HIV infections with a potential association to viremia in HIV-2; numbers of CD56bright NK cells were reduced in HIV infections, and did not differ between HIV-2 viremic and non-viremic individuals. Activation, assessed by CD38 expression, of iNKT and NK cells was increased in HIV infection, particularly in HIV-1 singly infected, and HIV-2 viremia associated with higher CD38 levels. iNKT and NK cell activation levels correlated also with % CD4+ T cells, HIV viral load, and CD4+ T cell activation. The expression of the PLZF transcription factor tended to be reduced in NK cells of HIV-D infected. T-bet expression was instead significantly higher in CD56bright NK cells during HIV-1 single infection.

Conclusions
Numbers of iNKT and NK cells are reduced in HIV infection, with HIV-2 viremia correlating with the loss of CD4+ iNKT and CD56dim NK cells. Elevated activation associates with HIV-1 infection and HIV-2 viremia, and correlates with CD4+ T cell level, viral load and CD4+ T cell activation. These cellular alterations may be linked to changes in development and function regulated by the expression of certain transcription factors, including PLZF and/or T-bet, which merit further studies.