Detection of high frequencies of HIV-1 cross-subtype reactive CD8 T lymphocytes in the peripheral blood of HIV-1-infected Kenyans

被引:19
作者
Currier, JR
Dowling, WE
Wasunna, KM
Alam, U
Masons, CJ
Robb, ML
Carr, JK
McCutchan, FE
Birx, DL
Cox, JH
机构
[1] US Mil HIV Res Program, Rockville, MD 20850 USA
[2] Kenya Govt Med Res Ctr, Clin Res Ctr, Nairobi, Kenya
[3] US Army Med Res Unit, Nairobi, Kenya
关键词
Africa; CD8 T cell; cross-subtype; full-length sequence; HIV-1; recombinant; subtype-specificity; VIRUS TYPE-1 HIV-1; RESPONSES; EPITOPES; IDENTIFICATION; AIDS; ELISPOT; ESCAPE; DEFINITION; DIVERSITY; PROTEINS;
D O I
10.1097/00002030-200310170-00002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objectives: To quantitate rapidly the frequency of HIV-1 subtype-specific and broadly HIV-1 cross-subtype-reactive CD8 T cells in the peripheral blood of HIV-1-infected individuals from a geographical region of multiple subtype endemicity. Methods: Autologous B-lymphoblastoid cell lines infected with recombinant vaccinia-viruses expressing gag, env and nef gene products from HIV-1 subtypes A-H were used as antigen-presenting cells to stimulate CD8 T cells from cryopreserved peripheral blood mononuclear cells. Cross-subtype and subtype-specific CD8 cell responses were assessed by flow cytometry for the upregulation of IFN-gamma gene expression in specifically activated CD8 T cells. Results: Strikingly high frequencies of circulating CD8 T cells (up to 11.3% of peripheral CD8 T cells) with specificity for HIV-1 were detectable using this methodology. Both subtype-specific and broadly cross-subtype-reactive CD8 T cells were detected as assessed by IFN-gamma production after stimulation. The pattern of cross-subtype reactivity appeared to be random when the results were assessed as a population, but analysis of the full-length sequence of the infecting virus for each individual showed some skewing of the CD8 cell response towards the infecting subtype. Conclusion: High frequencies of HIV-1 cross-subtype-reactive peripheral CD8 T cells can be detected in individuals from a multiple subtype endemic region, providing an incentive for vaccine advancement in such locations. The future assessment of the subtype specificity of cellular immune responses requires full-length sequencing of the infecting virus in conjunction with a comprehensive analysis of phenotypic and functional parameters. (C) 2003 Lippincott Williams Wilkins.
引用
收藏
页码:2149 / 2157
页数:9
相关论文
共 27 条
[1]   Identification of novel HLA-A2-restricted human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte epitopes predicted by the HLA-A2 supertype peptide-binding motif [J].
Altfeld, MA ;
Livingston, B ;
Reshamwala, N ;
Nguyen, PT ;
Addo, MM ;
Shea, A ;
Newman, M ;
Fikes, J ;
Sidney, J ;
Wentworth, P ;
Chesnut, R ;
Eldridge, RL ;
Rosenberg, ES ;
Robbins, GK ;
Brander, C ;
Sax, PE ;
Boswell, S ;
Flynn, T ;
Buchbinder, S ;
Goulder, PJR ;
Walker, BD ;
Sette, A ;
Kalams, SA .
JOURNAL OF VIROLOGY, 2001, 75 (03) :1301-1311
[2]   Identification of dominant optimal HLA-B60-and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: Rapid characterization of CTL responses by enzyme-linked immunospot assay [J].
Altfeld, MA ;
Trocha, A ;
Eldridge, RL ;
Rosenberg, ES ;
Phillips, MN ;
Addo, MM ;
Sekaly, RP ;
Kalams, SA ;
Burchett, SA ;
McIntosh, K ;
Walker, BD ;
Goulder, PJR .
JOURNAL OF VIROLOGY, 2000, 74 (18) :8541-8549
[3]   Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes [J].
Barouch, DH ;
Kunstman, J ;
Kuroda, MJ ;
Schmitz, JE ;
Santra, S ;
Peyerl, FW ;
Krivulka, GR ;
Beaudry, K ;
Lifton, MA ;
Gorgone, DA ;
Montefiori, DC ;
Lewis, MG ;
Wolinsky, SM ;
Letvin, NL .
NATURE, 2002, 415 (6869) :335-339
[4]   Cross-clade human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte responses in HIV-infected Zambians [J].
Betts, MR ;
Krowka, J ;
Santamaria, C ;
Balsamo, K ;
Gao, F ;
Mulundu, G ;
Luo, CW ;
NGandu, N ;
Sheppard, H ;
Hahn, BH ;
Allen, S ;
Frelinger, JA .
JOURNAL OF VIROLOGY, 1997, 71 (11) :8908-8911
[5]   Cellular immunity to human immunodeficiency virus type 1 (HIV-1) clades: Relevance to HIV-1 vaccine trials in Uganda [J].
Cao, HY ;
Mani, I ;
Vincent, R ;
Mugerwa, R ;
Mugyenyi, P ;
Kanki, P ;
Ellner, J ;
Walker, BD .
JOURNAL OF INFECTIOUS DISEASES, 2000, 182 (05) :1350-1356
[6]   Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: Implications for vaccine development [J].
Cao, HY ;
Kanki, P ;
Sankale, JL ;
DiengSarr, A ;
Mazzara, GP ;
Kalams, SA ;
Korber, B ;
Mboup, S ;
Walker, BD .
JOURNAL OF VIROLOGY, 1997, 71 (11) :8615-8623
[7]   Comprehensive screening for human immunodeficiency virus type 1 subtype-specific CD8 cytotoxic T lymphocytes and definition of degenerate epitopes restricted by HLA-A0207 and -Cw0304 Alleles [J].
Currier, JR ;
deSouza, M ;
Chanbancherd, P ;
Bernstein, W ;
Birx, DL ;
Cox, JH .
JOURNAL OF VIROLOGY, 2002, 76 (10) :4971-4986
[8]   Forty-one near full-length HIV-1 sequences from Kenya reveal an epidemic of subtype A and A-containing recombinants [J].
Dowling, WE ;
Kim, B ;
Mason, CJ ;
Wasunna, KM ;
Alam, U ;
Elson, L ;
Birx, DL ;
Robb, ML ;
McCutchan, FE ;
Carr, JK .
AIDS, 2002, 16 (13) :1809-1820
[9]   Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers [J].
Ferrari, G ;
Humphrey, W ;
McElrath, MJ ;
Excler, JL ;
Duliege, AM ;
Clements, ML ;
Corey, LC ;
Bolognesi, DP ;
Weinhold, KJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (04) :1396-1401
[10]   AIDS - Diversity considerations in HIV-1 vaccine selection [J].
Gaschen, B ;
Taylor, J ;
Yusim, K ;
Foley, B ;
Gao, F ;
Lang, D ;
Novitsky, V ;
Haynes, B ;
Hahn, BH ;
Bhattacharya, T ;
Korber, B .
SCIENCE, 2002, 296 (5577) :2354-2360