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Soluble PD‐1 rescues the proliferative response of simian immunodeficiency virus‐specific CD4 and CD8 T cells during chronic infection
Author(s) -
Onlamoon Nattawat,
Rogers Kenneth,
Mayne Ann E.,
Pattanapanyasat Kovit,
Mori Kazuyasu,
Villinger Francois,
Ansari Aftab A.
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02766.x
Subject(s) - simian immunodeficiency virus , immunodeficiency , virology , cd8 , simian , biology , human immunodeficiency virus (hiv) , cytotoxic t cell , immunology , virus , immune system , genetics , in vitro
Summary Phenotypic and functional studies of the programmed death‐1 (PD‐1) molecule on CD4 + and CD8 + T cells were performed on peripheral blood mononuclear cells from uninfected and simian immunodeficiency virus (SIV)‐infected rhesus macaques. These data demonstrated a rapid upregulation of PD‐1 expression on tetramer‐positive CD8 + T cells from MamuA.01 + SIV‐infected macaques upon infection. Upregulation of PD‐1 on total CD8 + T cells was not detectable. In contrast, CD4 + T‐cell PD‐1 expression was markedly higher in total CD4 + T cells during chronic, but not acute, infection and there was a correlation between the level of PD‐1 expression on naive and central memory CD4 + T cells and the levels of viral loads. Such association was emphasized further by a marked decrease of PD‐1 expression on tetramer‐positive CD8 T cells as well as on CD4 + T cells on longitudinal samples collected before and after the initiation of antiretroviral therapy and downregulation of viral replication in vivo . Cloning of PD‐1 and its two ligands from several non‐human primate species demonstrated > 95% conservation for PD‐1 and PD‐L2 and only about 91% homology for PD‐L1. Functional studies using soluble recombinant PD‐1 protein or PD‐1–immunoglobulin G fusion proteins induced marked increases in the SIV‐specific proliferative responses of both CD4 + and CD8 + T cells from rhesus macaques. The results of these studies serve as a foundation for future in vivo trials of the use of rMamu‐PD‐1 to potentially enhance and/or restore antiviral immune responses in vivo .