Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa following a pathogenic simian immunodeficiency virus infection correlates with diminished antiviral T cell response and viral control.
FOXP3(+)CD8(+) T cells are present at low levels in humans; however, the function of these cells is not known. In this study, we demonstrate a rapid expansion of CD25(+)FOXP3(+)CD8(+) regulatory T cells (Tregs) in the blood and multiple tissues following a pathogenic SIV infection in rhesus macaques. The expansion was pronounced in lymphoid and colorectal mucosal tissues, preferential sites of virus replication. These CD8 Tregs expressed molecules associated with immune suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV-specific T cells in vitro. They also expressed low levels of granzyme B and perforin, suggesting that these cells do not possess killing potential. Expansion of CD8 Tregs correlated directly with acute phase viremia and inversely with the magnitude of antiviral T cell response. Expansion was also observed in HIV-infected humans but not in SIV-infected sooty mangabeys with high viremia, suggesting a direct role for hyperimmune activation and an indirect role for viremia in the induction of these cells. These results suggest an important but previously unappreciated role for CD8 Tregs in suppressing antiviral immunity during immunodeficiency virus infections. These results also suggest that CD8 Tregs expand in pathogenic immunodeficiency virus infections in the nonnatural hosts and that therapeutic strategies that prevent expansion of these cells may enhance control of HIV infection.
Nigam
Pragati
P
Department of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Emory University, Atlanta, GA 30329, USA.
Velu
Vijayakumar
V
Kannanganat
Sunil
S
Chennareddi
Lakshmi
L
Kwa
Suefen
S
Siddiqui
Mariam
M
Amara
Rama Rao
RR
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016665:Cercocebus atys; D003106:Colon / Q000276:immunology / Q000473:pathology / Q000821:virology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D008253:Macaca mulatta; D012007:Rectum / Q000276:immunology / Q000473:pathology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014766:Viremia / Q000276:immunology / Q000473:pathology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit