title: Loss of IL-17-producing CD8 T cells during late chronic stage of pathogenic simian immunodeficiency virus infection.
abstract: Progressive disease caused by pathogenic SIV/HIV infections is marked by systemic hyperimmune activation, immune dysregulation, and profound depletion of CD4(+) T cells in lymphoid and gastrointestinal mucosal tissues. IL-17 is important for protective immunity against extracellular bacterial infections at mucosa and for maintenance of mucosal barrier. Although IL-17-secreting CD4 (Th17) and CD8 (Tc17) T cells have been reported, very little is known about the latter subset for any infectious disease. In this study, we characterized the anatomical distribution, phenotype, and functional quality of Tc17 and Th17 cells in healthy (SIV-) and SIV+ rhesus macaques. In healthy macaques, Tc17 and Th17 cells were present in all lymphoid and gastrointestinal tissues studied with predominance in small intestine. About 50% of these cells coexpressed TNF-α and IL-2. Notably, ∼50% of Tc17 cells also expressed the co-inhibitory molecule CTLA-4, and only a minority (<20%) expressed granzyme B suggesting that these cells possess more of a regulatory than cytotoxic phenotype. After SIV infection, unlike Th17 cells, Tc17 cells were not depleted during the acute phase of infection. However, the frequency of Tc17 cells in SIV-infected macaques with AIDS was lower compared with that in healthy macaques demonstrating the loss of these cells during end-stage disease. Antiretroviral therapy partially restored the frequency of Tc17 and Th17 cells in the colorectal mucosa. Depletion of Tc17 cells was not observed in colorectal mucosa of chronically infected SIV+ sooty mangabeys. In conclusion, our results suggest a role for Tc17 cells in regulating disease progression during pathogenic SIV infection.
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, GA 30329, USA.
authors.forename: Pragati
authors.initials: P
authors.lastname: Nigam
authors.forename: Suefen
authors.initials: S
authors.lastname: Kwa
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Velu
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
mesh_terms: D000208:Acute Disease; D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D016665:Cercocebus atys; D002908:Chronic Disease; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000172:deficiency* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D044966:Anti-Retroviral Agents; D020381:Interleukin-17; D007371:Interferon-gamma