Distribution and phenotype of HIV-specific CD8 T cells in situ in the rectal mucosa of HIV elite controllers

Abstract Mucosal tissues including the gastrointestinal tract are important reservoirs for HIV replication. HIV-specific CD8 T cells are essential in controlling HIV infection. In order to gain insights into HIV-specific CD8 T cells in elite controllers (EC), we characterized this important cell population in rectal biopsies from EC using in situ tetramer staining combined with immunohistochemistry followed by quantitative analysis. Results showed tetramer+ HIV-specific CD8 T cells distributed unevenly throughout the rectal mucosa including within lymphoid aggregates. Frequencies of tetramer+ HIV-specific CD8 T cells ranged from 2 to 25 cells/mm2. A mean of 55% tetramer+ HIV-specific CD8 T cells expressed the effector protein perforin. Among the perforin+ HIV-specific T cells, the majority expressed low to medium levels of perforin and relatively few expressed high levels. In addition, we also observed a subset of perforin+ HIV-specific CD8 T cells in which perforin was located exclusively within the cell membrane, possibly representing a novel subset of armed resident or effector memory cells. Almost all tetramer+ HIV-specific CD8 T cells in the rectal mucosa were negative for Ki67, a marker for activation and proliferation (mean of 96%); many were PD-1+, a marker for recent T cell stimulation or exhaustion (mean of 59%), and some expressed CD103, a marker for a subset of resident memory T cells (mean of 6%). Taken together, these findings indicate that EC maintain diverse populations of memory HIV-specific CD8 T cells distributed throughout the rectal mucosa including within lymphoid aggregates and suggests that these cells are likely continually being exposed to antigen, but not dividing.