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.
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.
Papasavvas
Emmanouil
E
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Moore
Elizabeth C
EC
Sun
Junwei
J
Azzoni
Livio
L
Pistilli
Maxwell
M
Mounzer
Karam
K
Shull
Jane
J
Kostman
Jay R
JR
Montaner
Luis J
LJ
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
D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D007371:Interferon-gamma
J Immunol. 1999 Jun 15;162(12):7534-42
10358209
Semin Arthritis Rheum. 2005 Dec;35(3):166-74
16325657
J Exp Med. 1997 Jan 6;185(1):55-64
8996241
AIDS Res Hum Retroviruses. 1996 Jul 1;12(10):885-92
8798973
AIDS. 1996 Jan;10(1):9-16
8924258
AIDS. 1992 Aug;6(8):793-7
1418775
Clin Exp Immunol. 1997 Jul;109(1):54-8
9218824
Clin Exp Immunol. 1994 Mar;95(3):436-41
7907956
J Clin Invest. 1989 Dec;84(6):1892-9
2574188
J Exp Med. 1994 Apr 1;179(4):1361-6
7908324
AIDS. 2002 Sep 27;16(14):1877-85
12351947
J Exp Med. 2003 Dec 15;198(12):1909-22
14676302
Nature. 1998 Sep 10;395(6698):189-94
9744279
Clin Exp Immunol. 2001 Aug;125(2):266-73
11529919
Science. 1997 Jul 4;277(5322):112-6
9204894
J Infect Dis. 1999 Feb;179(2):329-36
9878015
J Clin Immunol. 2000 Jan;20(1):62-7
10798609
Pediatr Res. 1998 Jun;43(6):752-8
9621984
J Infect Dis. 2000 Sep;182(3):766-75
10950770
Nat Med. 1999 May;5(5):518-25
10229228
Medicine (Baltimore). 2005 Mar;84(2):98-106
15758839
Clin Immunol Immunopathol. 1994 Apr;71(1):19-26
7511081
AIDS. 2004 Apr 30;18(7):981-9
15096800