Diminished viral control during simian immunodeficiency virus infection is associated with aberrant PD-1hi CD4 T cell enrichment in the lymphoid follicles of the rectal …

GH Mylvaganam, V Velu, JJ Hong… - The Journal of …, 2014 - journals.aai.org
GH Mylvaganam, V Velu, JJ Hong, S Sadagopal, S Kwa, R Basu, B Lawson, F Villinger…
The Journal of Immunology, 2014journals.aai.org
The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell
function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-
associated lymphoid tissue, is less well understood. In this study, we show that a subset of
CD4 T cells expresses high levels of PD-1 (PD-1 hi) in the rectal mucosa, a preferential site
of virus replication. The majority of these PD-1 hi CD4 T cells expressed Bcl-6 and CXCR5,
markers characteristic of T follicular helper cells in the lymph nodes. Following a pathogenic …
Abstract
The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood. In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1 hi) in the rectal mucosa, a preferential site of virus replication. The majority of these PD-1 hi CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes. Following a pathogenic SIV infection, the frequency of PD-1 hi cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5. Furthermore, only a small fraction of PD-1 hi cells expressed CCR5, and despite this low level of viral coreceptor expression, a significant fraction of these cells were productively infected. Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1 hi CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B+ CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1 hi CD4 T cells. These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV+ PD-1 hi CD4 T cells at mucosal sites as a means to enhance viral control.
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