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
Volume10
Issue12
Paginatione0144767
Date Published2015
ISSN1932-6203
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
Abstract

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.

DOI10.1371/journal.pone.0144767
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