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Selective Loss of Early Differentiated, Highly Functional PD1.sup.high CD4 T Cells with HIV Progression
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Selective Loss of Early Differentiated, Highly Functional PD1.sup.high CD4 T Cells with HIV Progression
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Journal Article
Selective Loss of Early Differentiated, Highly Functional PD1.sup.high CD4 T Cells with HIV Progression
2015
Overview
The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127.sup.high CD4 T cells within the early/intermediate differentiated (EI) (CD27.sup.high CD45RA.sup.low) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1.sup.high CTLA-4.sup.low CD4 T cells was found specifically in the CD127.sup.high CD27.sup.high CD45RA.sup.low compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1.sup.high compared to PD-1.sup.low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1.sup.low EI CD4 T cells. In line with our previous findings, PD-1.sup.high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection.
Publisher
Public Library of Science
