title: HIV-specific T-cell responses detected in the genital tract of chronically HIV-infected women are largely monofunctional.
abstract: HIV-specific T cells that produce interferon-γ (IFN-γ) are present in the genital tract of HIV-infected women although these do not provide protection against genital HIV shedding. Because polyfunctional HIV-specific T cells have been implicated in better HIV control than those with a single function, this study aimed to investigate whether polyfunctional T cells were present at the female genital mucosa. Cervical cytobrush-derived T cells were obtained from chronically HIV-infected women and compared with blood. CD3(+) T cells from both compartments were expanded with Dynal anti-CD3/CD28 expander beads for 14 days and flow cytometry was used to evaluate four T-cell functions (CD107a, IFN-γ, tumour necrosis factor-α and macrophage inflammatory protein-1β) from 16 women. The majority of Gag-specific T-cell responses in the female genital tract were monofunctional, although low frequencies of HIV Gag-specific polyfunctional CD8(+) T cells were detected at the cervix in 81·3% (13/16) of women. The ability of CD8(+) T cells at both the cervix and in blood to express CD107a and to exhibit polyfunctional responses (two or more functions) following Gag stimulation was inversely associated with plasma viral load and positively associated with blood CD4 counts, suggesting that clinical status impacted on the functionality of HIV-specific T cells at the mucosa, in a similar way to blood. HIV Gag-specific cervical T cells were largely monofunctional. Polyfunctional T cells were detected at the cervix in women with high blood CD4 count and low plasma viral load but these did not protect from HIV genital shedding.
authors: Division of Medical Virology, Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Alfred
authors: A
authors: Bere
authors: Lynette
authors: L
authors: Denny
authors: Prinola
authors: P
authors: Naicker
authors: Wendy A
authors: WA
authors: Burgers
authors: Jo-Ann S
authors: JA
authors: Passmore
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D002584:Cervix Uteri / Q000276:immunology* / Q000821:virology; D054407:Chemokine CCL4 / Q000378:metabolism; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D054407:Chemokine CCL4; D052118:Lysosomal-Associated Membrane Protein 1; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma
references: Cytometry A. 2011 Feb;79(2):167-74
references: 21265010
references: Immunology. 2006 Dec;119(4):507-14
references: 17026720
references: J Virol. 2007 Jun;81(11):5460-71
references: 17344302
references: Eur J Immunol. 2008 Feb;38(2):350-63
references: 18200635
references: J Virol. 2004 May;78(9):4463-77
references: 15078927
references: Immunol Lett. 2001 Nov 1;79(1-2):117-25
references: 11595298
references: J Virol. 2002 Mar;76(5):2298-305
references: 11836408
references: J Immunol Methods. 2003 Aug;279(1-2):17-31
references: 12969544
references: J Virol. 2003 Feb;77(3):2081-92
references: 12525643
references: J Virol. 2005 Apr;79(7):4289-97
references: 15767429
references: J Virol. 1994 Sep;68(9):6103-10
references: 8057491
references: J Immunol Methods. 2010 Mar 31;354(1-2):68-79
references: 20149794
references: Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1890-5
references: 9050875
references: J Clin Invest. 1999 Nov;104(10):1431-9
references: 10562305
references: Mucosal Immunol. 2008 Nov;1(6):475-88
references: 19079215
references: Blood. 2009 Apr 23;113(17):3978-89
references: 19109229
references: Immunology. 2009 Sep;128(1 Suppl):e746-57
references: 19740336
references: J Immunol Methods. 2011 Mar 31;367(1-2):47-55
references: 21324321
references: J Immunol Methods. 2002 Apr 1;262(1-2):71-83
references: 11983220
references: Virology. 2000 May 10;270(2):317-27
references: 10792991
references: J Infect Dis. 2005 Nov 1;192(9):1588-96
references: 16206073
references: J Exp Med. 1999 Mar 15;189(6):991-8
references: 10075982
references: Nat Med. 2007 Jul;13(7):843-50
references: 17558415
references: Nat Immunol. 2006 Mar;7(3):235-9
references: 16482171
references: J Infect Dis. 2005 Sep 1;192(5):728-38
references: 16088822
references: Nat Med. 1997 Feb;3(2):212-7
references: 9018241
references: J Immunol. 2000 Feb 1;164(3):1602-11
references: 10640781
references: Immunology. 2010 May;130(1):23-33
references: 20201983
references: AIDS. 1998 Aug 20;12(12):1561-3
references: 9727585
references: J Exp Med. 2007 Oct 1;204(10):2473-85
references: 17893201
references: J Exp Med. 2007 Jun 11;204(6):1405-16
references: 17535971
references: Blood. 2006 Jun 15;107(12):4781-9
references: 16467198
references: Mucosal Immunol. 2008 Jan;1(1):49-58
references: 19079160
references: J Immunol. 2002 Dec 1;169(11):6376-85
references: 12444145
references: J Virol. 1994 Jul;68(7):4650-5
references: 8207839
references: J Virol. 2008 Sep;82(17):8529-36
references: 18562528