Highly avid, oligoclonal, early-differentiated antigen-specific CD8+ T cells in chronic HIV-2 infection.
HIV-1-specific CD8(+) T cells are present in most HIV-1-infected people and play an important role in controlling viral replication, but the characteristics of an effective HIV-specific T-cell response are largely unknown. The majority of HIV-2-infected people behave as long-term non-progressors while those who progress to AIDS do so in a manner indistinguishable from HIV-1. A detailed study of HIV-2 infection may identify protective immune responses. Robust gag p26-specific T-cell responses are elicited during HIV-2 infection and correlate with control of viremia. In this study, we analyzed features of an HLA-B 3501-restricted T-cell response to HIV-2 p26 that may contribute to virus control. In contrast to HIV-1, HIV-2-specific T cells are at an early stage of differentiation (CD27(+)CD28(+)), a finding that relates directly to CD4(+) T-cell levels and inversely to immune activation. The cells demonstrate IFN-gamma secretion, oligoclonal T-cell receptor Vbeta gene segment usage, exceptional avidity and secretion of pro-inflammatory cytokines. Despite the potentially strong selection pressure imposed on the virus by these cells, there was no evidence of HIV-2 sequence evolution. We propose that in chronic HIV-2 infection, the maintenance of early-differentiated, highly avid CD8(+) T cells could account for the non-progressive course of disease. Such responses may be desirable from an HIV vaccine.
Leligdowicz
Aleksandra
A
Weatherall Institute of Molecular Medicine, Medical Research Council Human Immunology Unit, John Radcliffe Hospital, Oxford, UK. aleksandra.leligdowicz@mail.mcgill.ca
Onyango
Clayton
C
Yindom
Louis-Marie
LM
Peng
Yanchun
Y
Cotten
Matthew
M
Jaye
Assan
A
McMichael
Andrew
A
Whittle
Hilton
H
Dong
Tao
T
Rowland-Jones
Sarah
S
D016915:AIDS Vaccines; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D002908:Chronic Disease; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D019672:Genes, T-Cell Receptor / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015498:HIV-2 / Q000276:immunology*; D015235:HLA-B Antigens / Q000378:metabolism; D015797:HLA-B35 Antigen; D006650:Histocompatibility Testing; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D015703:Antigens, CD; D000943:Antigens, Differentiation; D016207:Cytokines; D015235:HLA-B Antigens; C500431:HLA-B*35:01 antigen; D015797:HLA-B35 Antigen; D054301:gag Gene Products, Human Immunodeficiency Virus; C065558:gag protein p26, Human immunodeficiency virus