Qualitative features of the HIV-specific CD8+ T-cell response associated with immunologic control

被引:79
作者
Hersperger, Adam R. [2 ]
Migueles, Stephen A. [1 ]
Betts, Michael R. [2 ]
Connors, Mark [1 ]
机构
[1] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA
[2] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
关键词
CD8(+) T cells; cytotoxicity; elite controllers; long-term nonprogressors; perforin; IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL REPLICATION CAPACITY; LONG-TERM NONPROGRESSORS; PERFORIN EXPRESSION; CYTOTOXIC GRANULES; ELITE SUPPRESSORS; IMMUNE CONTROL; UP-REGULATION; INFECTION; MEMORY;
D O I
10.1097/COH.0b013e3283454c39
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Purpose of review Over the past 2 years, a clearer picture has emerged regarding the properties of HIV-specific CD8(+) T cells associated with immunologic control of HIV replication. These properties represent a potential mechanism by which rare patients might control HIV replication in the absence of antiretroviral therapy. This review addresses the background and recent findings that have lead to our current understanding of these mechanism(s). Recent findings Patients with immunologic control of HIV are not distinguished by targeted specificities, or greater numbers or breadth of their HIV-specific CD8(+) T-cell response. For this reason, recent work has focused greater attention on qualitative features of this response. The qualitative features most closely associated with immunologic control of HIV are related to the granule-exocytosis-mediated elimination of HIV-infected CD4(+) T cells. The ability of HIV-specific CD8(+) T cells to increase their contents of proteins known to mediate cytotoxicity, such as granzyme B and perforin, appears to be a critical means by which HIV-specific cytotoxic capacity is regulated. Summary Investigation from multiple groups has now focused upon HIV-specific CD8(+) T-cell granule-exocytosis-mediated cytotoxicity as a correlate of immunologic control of HIV. In the near future, a more detailed understanding of the qualities associated with immunologic control may provide critical insights regarding the necessary features of a response that should be stimulated by immunotherapies or T-cell-based vaccines.
引用
收藏
页码:169 / 173
页数:5
相关论文
共 58 条
[1]   Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection [J].
Altfeld, M ;
Addo, MA ;
Rosenberg, ES ;
Hecht, FA ;
Lee, PK ;
Vogel, M ;
Yu, XG ;
Draenert, R ;
Johnston, MN ;
Strick, D ;
Allen, TA ;
Feeney, ME ;
Kahn, JO ;
Sekaly, RP ;
Levy, JA ;
Rockstroh, JK ;
Goulder, PJR ;
Walker, BD .
AIDS, 2003, 17 (18) :2581-2591
[2]   Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections [J].
Appay, V ;
Dunbar, PR ;
Callan, M ;
Klenerman, P ;
Gillespie, GMA ;
Papagno, L ;
Ogg, GS ;
King, A ;
Lechner, F ;
Spina, CA ;
Little, S ;
Havlir, DV ;
Richman, DD ;
Gruener, N ;
Pape, G ;
Waters, A ;
Easterbrook, P ;
Salio, M ;
Cerundolo, V ;
McMichael, AJ ;
Rowland-Jones, SL .
NATURE MEDICINE, 2002, 8 (04) :379-385
[3]   HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function [J].
Appay, V ;
Nixon, DF ;
Donahoe, SM ;
Gillespie, GMA ;
Dong, T ;
King, A ;
Ogg, GS ;
Spiegel, HML ;
Conlon, C ;
Spina, CA ;
Havlir, DV ;
Richman, DD ;
Waters, A ;
Easterbrook, P ;
McMichael, AJ ;
Rowland-Jones, SL .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :63-75
[4]   CD8+ T cells from most HIV-1-infected patients, even when challenged with mature dendritic cells, lack functional recall memory to HIV gag but not other viruses [J].
Arrode, G ;
Finke, JS ;
Zebroski, H ;
Siegal, FP ;
Steinman, RM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (01) :159-170
[5]   Transmission of human immunodeficiency virus type 1 from a patient who developed AIDS to an elite suppressor [J].
Bailey, Justin R. ;
O'Connell, Karen ;
Yang, Hung-Chih ;
Han, Yefei ;
Xu, Jie ;
Jilek, Benjamin ;
Williams, Thomas M. ;
Ray, Stuart C. ;
Siliciano, Robert F. ;
Blankson, Joel N. .
JOURNAL OF VIROLOGY, 2008, 82 (15) :7395-7410
[6]   Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations [J].
Bailey, Justin R. ;
Williams, Thomas M. ;
Siliciano, Robert F. ;
Blankson, Joel N. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (05) :1357-1369
[7]   HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells [J].
Betts, Michael R. ;
Nason, Martha C. ;
West, Sadie M. ;
De Rosa, Stephen C. ;
Migueles, Stephen A. ;
Abraham, Jonathan ;
Lederman, Michael M. ;
Benito, Jose M. ;
Goepfert, Paul A. ;
Connors, Mark ;
Roederer, Mario ;
Koup, Richard A. .
BLOOD, 2006, 107 (12) :4781-4789
[8]   Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses:: Relationship to viral load in untreated HIV infection [J].
Betts, MR ;
Ambrozak, DR ;
Douek, DC ;
Bonhoeffer, S ;
Brenchley, JM ;
Casazza, JP ;
Koup, RA ;
Picker, LJ .
JOURNAL OF VIROLOGY, 2001, 75 (24) :11983-11991
[9]   Isolation and characterization of replication-competent human immunodeficiency virus type 1 from a subset of elite suppressors [J].
Blankson, Joel N. ;
Bailey, Justin R. ;
Thayil, Seema ;
Yang, Hung-Chih ;
Lassen, Kara ;
Lai, Jun ;
Gandhi, Shiv K. ;
Siliciano, Janet D. ;
Williams, Thomas M. ;
Siliciano, Robert F. .
JOURNAL OF VIROLOGY, 2007, 81 (05) :2508-2518
[10]   Escape and compensation from early HLA-B57-Mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A [J].
Brockman, Mark A. ;
Schneidewind, Arne ;
Lahaie, Matthew ;
Schmidt, Aaron ;
Miura, Toshiyuki ;
DeSouza, Ivna ;
Ryvkin, Faina ;
Derdeyn, Cynthia A. ;
Allen, Susan ;
Hunter, Eric ;
Mulenga, Joseph ;
Goepfert, Paul A. ;
Walker, Bruce D. ;
Allen, Todd M. .
JOURNAL OF VIROLOGY, 2007, 81 (22) :12608-12618