Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression.

TitleSelective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression.
Publication TypeJournal Article
Year of Publication2015
AuthorsParis RM, Petrovas C, Ferrando-Martinez S, Moysi E, Boswell KL, Archer E, Yamamoto T, Ambrozak D, Casazza JP, Haubrich R, Connors M, Ake J, Kim JH, Koup RA
JournalPLoS One
Date Published2015
KeywordsAnti-HIV Agents, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Cytokines, Disease Progression, Flow Cytometry, HIV Infections, HIV-1, Humans, Polymerase Chain Reaction, Programmed Cell Death 1 Receptor, Receptors, CCR5, Viral Load

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 CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) 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-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow 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-1high compared to PD-1low 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-1low EI CD4 T cells. In line with our previous findings, PD-1high 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.

Alternate JournalPLoS ONE
PubMed ID26678998
PubMed Central IDPMC4692060
Grant ListAI064086 / AI / NIAID NIH HHS / United States
AI36214 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
Y1-AI-2642-12 / AI / NIAID NIH HHS / United States
/ / Intramural NIH HHS / United States