title: Simian immunodeficiency virus infection and immune responses in the pig-tailed macaque testis.
abstract: The testis is a site of immune privilege in rodents, and there is evidence that T cell responses are also suppressed in the primate testis. Local immunosuppression is a potential mechanism for HIV persistence in tissue reservoirs that few studies have examined. The response of the pig-tailed macaque testis to SIVmac239 infection was characterized to test this possibility. Testes were surgically removed during early-chronic (10 wk) and late-chronic (24-30 wk) SIV infection in 4 animals and compared with those from 7 uninfected animals. SIV infection caused only minor disruption to the seminiferous epithelium without marked evidence of inflammation or consistent changes in total intratesticular leukocyte numbers. Infection also led to an increase in the relative proportion of testicular effector memory CD8(+) T cell numbers and a corresponding reduction in central memory CD4(+) T cells. A decrease in the relative proportion of resident-type CD163(+) macrophages and DCs was also observed. SIV-specific CD8(+) T cells were detectable in the testis, 10-11 wk after infection by staining with SIV Gag-specific or Tat-specific MHC-I tetramers. However, testicular CD8(+) T cells from the infected animals had suppressed cytokine responses to mitogen activation. These results support the possibility that local immunosuppression in the testis may be restricting the ability of T cells to respond to SIV or HIV infection. Local immunosuppression in the testis may be an underexplored mechanism allowing HIV persistence.
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia wwinnall@unimelb.edu.au.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Winnall
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Lloyd
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Sheilajen
authors.initials: S
authors.lastname: Alcantara
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Thakshila H
authors.initials: TH
authors.lastname: Amarasena
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hedger
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Girling
authors.affiliation: *Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Centre for Reproductive Health, Monash Institute of Medical Research-Prince Henry's Institute of Medical Research, Victoria, Australia; and Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000473:pathology; D006098:Granulocytes / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007109:Immunity; D007694:Killer Cells, Natural / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008254:Macaca nemestrina / Q000276:immunology* / Q000821:virology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D010641:Phenotype; D012671:Seminiferous Tubules / Q000276:immunology / Q000473:pathology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013737:Testis / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D016207:Cytokines; D017493:Leukocyte Common Antigens
keywords: CD4+ T cells; CD8+ T cells; HIV; immune privilege; testicular macrophages