title: Foreskin T-cell subsets differ substantially from blood with respect to HIV co-receptor expression, inflammatory profile, and memory status.
abstract: The foreskin is the main site of heterosexual human immunodeficiency virus (HIV) acquisition in uncircumcised men, but functional data regarding T-cell subsets present at this site are lacking. Foreskin tissue and blood were obtained from Ugandan men undergoing elective adult circumcision. Tissue was treated by mechanical and enzymatic digestion followed by T-cell subset identification and assessment of cytokine production using flow cytometry. Foreskin CD4(+) T cells were predominantly an effector memory phenotype, and compared with blood they displayed a higher frequency of CCR5 expression (42.0% vs. 9.9%) and interleukin-17 production. There was no difference in T-regulatory cell frequency, but interferon-γ and tumor necrosis factor-α production were increased in foreskin CD8(+) T cells. These novel techniques demonstrate that the foreskin represents a proinflammatory milieu that is enriched for HIV-susceptible T-cell subsets. Further characterization of foreskin T-cell subsets may help to define the correlates of HIV susceptibility in the foreskin.
authors.affiliation: Clinical Science Division, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Prodger
authors.forename: R
authors.initials: R
authors.lastname: Gray
authors.forename: G
authors.initials: G
authors.lastname: Kigozi
authors.forename: F
authors.initials: F
authors.lastname: Nalugoda
authors.forename: R
authors.initials: R
authors.lastname: Galiwango
authors.forename: T
authors.initials: T
authors.lastname: Hirbod
authors.forename: M
authors.initials: M
authors.lastname: Wawer
authors.forename: S O P
authors.initials: SO
authors.lastname: Hofer
authors.forename: N
authors.initials: N
authors.lastname: Sewankambo
authors.forename: D
authors.initials: D
authors.lastname: Serwadda
authors.forename: R
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000293:Adolescent; D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004198:Disease Susceptibility; D005434:Flow Cytometry; D052816:Foreskin / Q000166:cytology / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014454:Uganda; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D019713:Receptors, CCR5
references.citation: Am J Reprod Immunol. 2011 Mar;65(3):279-83
references.pmid: 21114567
references.citation: Nature. 1999 Oct 14;401(6754):708-12
references.pmid: 10537110
references.citation: Annu Rev Immunol. 2007;25:297-336
references.pmid: 17150027
references.citation: J Reprod Immunol. 2008 Jan;77(1):32-40
references.pmid: 17395270
references.citation: Mucosal Immunol. 2010 Sep;3(5):506-22
references.pmid: 20571487
references.citation: Nature. 2009 Apr 23;458(7241):1034-8
references.pmid: 19262509
references.citation: Annu Rev Med. 2011;62:127-39
references.pmid: 21054171
references.citation: AIDS. 2006 Jan 2;20(1):73-83
references.pmid: 16327322
references.citation: Am J Reprod Immunol. 2011 Mar;65(3):220-9
references.pmid: 21214659
references.citation: Immunology. 1995 Jul;85(3):475-84
references.pmid: 7558138
references.citation: J Infect Dis. 2010 Mar 15;201(6):843-54
references.pmid: 20144043
references.citation: AIDS. 2006 Jul 13;20(11):1491-5
references.pmid: 16847403
references.citation: AIDS. 2009 Oct 23;23(16):2209-13
references.pmid: 19770623
references.citation: AIDS. 2000 Oct 20;14(15):2371-81
references.pmid: 11089626
references.citation: J Infect Dis. 2009 May 1;199(9):1318-22
references.pmid: 19301980
references.citation: J Infect Dis. 2010 May 15;201(10):1455-62
references.pmid: 20370483
references.citation: J Immunol. 2011 Dec 1;187(11):6032-42
references.pmid: 22048765
references.citation: Clin Exp Immunol. 2006 Mar;143(3):435-44
references.pmid: 16487242
references.citation: J Infect Dis. 2009 Apr 1;199(7):945-9
references.pmid: 19220138
references.citation: J Transl Med. 2011 Jan 27;9 Suppl 1:S6
references.pmid: 21284905
references.citation: Am J Clin Pathol. 2006 Mar;125(3):386-91
references.pmid: 16613341
references.citation: Int Urol Nephrol. 2009 Dec;41(4):747-53
references.pmid: 19184514
references.citation: Science. 1999 Nov 12;286(5443):1353-7
references.pmid: 10558989
references.citation: Am J Pathol. 2010 Jun;176(6):2798-805
references.pmid: 20395432
references.citation: AIDS. 2009 Jan 28;23(3):319-28
references.pmid: 19114867
references.citation: J Infect Dis. 2010 Nov 1;202 Suppl 3:S339-44
references.pmid: 20887221
references.citation: Retrovirology. 2006 Jun 22;3:35
references.pmid: 16792805
references.citation: J Immunol. 2010 Feb 1;184(3):1604-16
references.pmid: 20042588
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5640-5
references.pmid: 15064398
references.citation: Lancet. 2007 Feb 24;369(9562):657-66
references.pmid: 17321311
references.citation: Curr Opin HIV AIDS. 2010 Mar;5(2):151-7
references.pmid: 20543593
references.citation: PLoS Med. 2005 Nov;2(11):e298
references.pmid: 16231970
references.citation: Blood. 2007 May 1;109(9):4071-9
references.pmid: 17197428
references.citation: AIDS. 2010 Mar 27;24(6):899-906
references.pmid: 20098294
references.citation: Am J Reprod Immunol. 2011 Mar;65(3):284-91
references.pmid: 21114566
references.citation: Mucosal Immunol. 2010 Jul;3(4):410-8
references.pmid: 20410876
references.citation: Nat Immunol. 2010 Jun;11(6):471-6
references.pmid: 20485275
references.citation: Int Immunopharmacol. 2008 Oct;8(10):1338-43
references.pmid: 18687296
references.citation: Am J Pathol. 2002 Sep;161(3):867-73
references.pmid: 12213715
references.citation: J Immunol. 2000 Feb 1;164(3):1602-11
references.pmid: 10640781
references.citation: J Acquir Immune Defic Syndr. 2009 May 1;51(1):108-10
references.pmid: 19390332
references.citation: J Infect Dis. 2011 Mar 1;203(5):602-9
references.pmid: 21220779
references.citation: Lancet. 2007 Feb 24;369(9562):643-56
references.pmid: 17321310
references.citation: Nat Med. 2009 Aug;15(8):886-92
references.pmid: 19648930
references.citation: PLoS Pathog. 2011 Jun;7(6):e1002100
references.pmid: 21738469
references.citation: AIDS. 2007 Mar 12;21(5):589-98
references.pmid: 17314521
references.citation: AIDS. 2011 Mar 27;25(6):741-9
references.pmid: 21378536
references.citation: J Clin Invest. 2011 Mar;121(3):1102-10
references.pmid: 21317533