title: HIV type 1 viremia on ART is positively associated with polyclonal T cell proliferation in subjects with T cell IFN-gamma secretion levels comparable to those of uninfected subjects.
abstract: We investigated the association between plasma HIV-1 RNA, immune activation, and polyclonal T cell function in viremic subjects whether on or off antiretroviral therapy (ART). The surface expression of activation/functional molecules on T cells and monocytes as well as cytokine secretion and T cell proliferation were assessed in 23 HIV-1(-) and 79 HIV-1(+)-infected subjects with different levels of viral suppression and CD4(+) T cell count >250 cells/mm(3) for >6 months. Viral replication was associated with increased T cell and monocyte activation irrespective of ART. In subjects with a detectable viral load on ART, we found a positive association with anti-CD3/CD28-induced T cell proliferation compared to patients with undetectable viral load (<400 copies/ml). No difference among groups was observed for anti-CD3/CD28-mediated IFN-gamma responses. The presence of an unexpected positive association between polyclonal T cell proliferation and viral load in subjects with levels of T cell IFN-gamma responses comparable to those of uninfected subjects is of potential relevance to an increase in T cell activation response before the loss of polyclonal cytokine secretion and proliferation observed with disease progression. This finding suggests that T cell hyperresponsiveness may play a role in the pathogenesis of immune comorbidities on ART.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Papasavvas
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Moore
authors.forename: Junwei
authors.initials: J
authors.lastname: Sun
authors.forename: Livio
authors.initials: L
authors.lastname: Azzoni
authors.forename: Maxwell
authors.initials: M
authors.lastname: Pistilli
authors.forename: Karam
authors.initials: K
authors.lastname: Mounzer
authors.forename: Jane
authors.initials: J
authors.lastname: Shull
authors.forename: Jay R
authors.initials: JR
authors.lastname: Kostman
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D013223:Statistics as Topic; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D019562:Viral Load; D014766:Viremia
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D007371:Interferon-gamma
references.citation: J Immunol. 1999 Jun 15;162(12):7534-42
references.pmid: 10358209
references.citation: Semin Arthritis Rheum. 2005 Dec;35(3):166-74
references.pmid: 16325657
references.citation: J Exp Med. 1997 Jan 6;185(1):55-64
references.pmid: 8996241
references.citation: AIDS Res Hum Retroviruses. 1996 Jul 1;12(10):885-92
references.pmid: 8798973
references.citation: AIDS. 1996 Jan;10(1):9-16
references.pmid: 8924258
references.citation: AIDS. 1992 Aug;6(8):793-7
references.pmid: 1418775
references.citation: Clin Exp Immunol. 1997 Jul;109(1):54-8
references.pmid: 9218824
references.citation: Clin Exp Immunol. 1994 Mar;95(3):436-41
references.pmid: 7907956
references.citation: J Clin Invest. 1989 Dec;84(6):1892-9
references.pmid: 2574188
references.citation: J Exp Med. 1994 Apr 1;179(4):1361-6
references.pmid: 7908324
references.citation: AIDS. 2002 Sep 27;16(14):1877-85
references.pmid: 12351947
references.citation: J Exp Med. 2003 Dec 15;198(12):1909-22
references.pmid: 14676302
references.citation: Nature. 1998 Sep 10;395(6698):189-94
references.pmid: 9744279
references.citation: Clin Exp Immunol. 2001 Aug;125(2):266-73
references.pmid: 11529919
references.citation: Science. 1997 Jul 4;277(5322):112-6
references.pmid: 9204894
references.citation: J Infect Dis. 1999 Feb;179(2):329-36
references.pmid: 9878015
references.citation: J Clin Immunol. 2000 Jan;20(1):62-7
references.pmid: 10798609
references.citation: Pediatr Res. 1998 Jun;43(6):752-8
references.pmid: 9621984
references.citation: J Infect Dis. 2000 Sep;182(3):766-75
references.pmid: 10950770
references.citation: Nat Med. 1999 May;5(5):518-25
references.pmid: 10229228
references.citation: Medicine (Baltimore). 2005 Mar;84(2):98-106
references.pmid: 15758839
references.citation: Clin Immunol Immunopathol. 1994 Apr;71(1):19-26
references.pmid: 7511081
references.citation: AIDS. 2004 Apr 30;18(7):981-9
references.pmid: 15096800