Differential localization and limited cytotoxic potential of duodenal CD8+Tcells

The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8+ T cells. The role of duodenal Trm CD8+ T cells in viral control is still not well defined. We examined the spatial localization, phenotype, and function of CD8+ T cells in the human duodenal tissue from people living with HIV (PLHIV) and healthy controls. We found that Trm (CD69+CD103hi) cells were the predominant CD8+ T cell population in the duodenum. Immunofluorescence imaging of the duodenal tissue revealed that T cells were mostly localized in the lamina propria (LP). Furthermore, HIV-specific CD8+ T cells were enriched in the CD69+CD103-/lo population. However, the duodenal HIV-specific CD8+ Trm cells rarely expressed canonical molecules for potent cytolytic function (perforin and granzyme B) but were more polyfunctional than those from peripheral blood. Taken together, our results show that separated from HIV-susceptible LP CD4+ T cells. This could contribute to HIV persistence in the duodenum and provides critical information for the design of cure therapies. the Wellcome Trust (grant 107752/Z/15/Z) and the UK government The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust, or the UK government.

Automated summary

The duodenum serves as a major site of HIV persistence during suppressive antiretroviral therapy, with tissue-resident memory (Trm) CD8+ T cells playing a significant role. HIV-specific CD8+ Trm cells in the duodenum are enriched and exhibit high polyfunctionality but lack expression of canonical cytolytic molecules. These findings shed light on the mechanisms of HIV persistence in the duodenum and have implications for cure therapies.