IL-27 effects on HIVGag-specific CD4 and CD8 T cell function

Marta Catalfamo^1*Maryam Abdussamad¹Jie Cheng¹Grace Katz¹Chinmayee Mehta¹Fernando Andres-Martin¹Danial Mahmood²Princy Kumar²

• ¹Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, United States
• ²Division of Infectious Disease and Travel Medicine, Department of Medicine, Georgetown University Medical Center, Washington, DC, District of Columbia, United States

In people with HIV (PWH) and suppressed viral replication by antiretroviral therapy persistent T cell activation and inflammation are important contributors of the increased risk of morbidity and mortality. CD8 T cells express checkpoint receptors and are dysfunctional. IL-27, a member of the IL-6/IL-12 family has shown anti-viral properties against various human viruses, including HIV. The role of IL-27 on HIV-specific T cells remains unclear. We hypothesized that IL-27 will enhance the function of HIV-specific T cells and evaluated its effects on cytokine secretion, proliferation, and cytotoxicity. Our findings show that IL-27 upregulates cytokine secretion and cytotoxic potential, and trafficking of proliferating HIV-specific CD8 T cells expressing check point receptors TIGIT and PD-1. Unbiased clustering analysis showed that IL-27 may have differential effects on distinct populations of HIV-specific T cells. Altogether these results suggest that IL-27 may enhance T cell function in the setting of chronic HIV infection.