Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy

被引:436
作者
Pereyra, Florencia [1 ,2 ,3 ]
Addo, Marylyn M. [1 ,2 ]
Kaufmann, Daniel E. [1 ,2 ]
Liu, Yang [6 ]
Miura, Toshiyuki [1 ,2 ]
Rathod, Almas [1 ,2 ]
Baker, Brett [1 ,2 ]
Trocha, Alicja [1 ,2 ,5 ]
Rosenberg, Rachel [1 ,2 ]
Mackey, Elizabeth [1 ,2 ]
Ueda, Peggy [1 ,2 ]
Lu, Zhigang [1 ,2 ]
Cohen, Daniel [4 ]
Wrin, Terri [6 ]
Petropoulos, Christos J. [6 ]
Rosenberg, Eric S. [1 ,2 ]
Walker, Bruce D. [1 ,2 ,5 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA
[2] Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA
[3] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA
[4] Fenway Community Hlth Care Ctr, Boston, MA USA
[5] Howard Hughes Med Inst, Chevy Chase, MD USA
[6] Monogram Biosci, San Francisco, CA USA
关键词
D O I
10.1086/526786
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Spontaneous control of human immunodeficiency virus (HIV) infection has been documented in a minority of HIV-infected individuals. The mechanisms behind this outcome remain largely unknown, and a better understanding of them will likely influence future vaccine strategies. Methods. HIV-specific T cell and antibody responses as well as host genetics were examined in untreated HIV-infected patients who maintain comparatively low plasma HIV RNA levels (hereafter, controllers), including those with levels of < 50 RNA copies/mL (elite controllers, n = 64), those with levels of 50-2000 copies/mL (viremic controllers, n = 60); we also examined HIV-specific T cell and antibody responses as well as host genetics for patients with levels of > 10,000 copies/mL (chronic progressors, n = 30). Results. CD8 + T cells from both controller groups preferentially target Gag over other proteins in the context of diverse HLA class I alleles, whereas responses are more broadly distributed in persons with progressive infection. Elite controllers represent a distinct group of individuals who have significantly more CD4 and CD8 T cells that secrete interferon-gamma and interleukin-2 and lower levels of HIV-neutralizing antibodies. Individual responses were quite heterogeneous, and none of the parameters evaluated was uniquely associated with the ability to control viremia. Conclusions. Elite controllers are a distinct group, even when compared to persons with low level viremia, but they exhibit marked genetic and immunologic heterogeneity. Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies.
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收藏
页码:563 / 571
页数:9
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