Activation of CD8+ T lymphocytes through the T cell receptor turns on CD4 gene expression:: Implications for HIV pathogenesis

被引:121
作者
Flamand, L
Crowley, RW
Lusso, P
Colombini-Hatch, S
Margolis, DM
Gallo, RC
机构
[1] Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA
[2] San Raffaele Sci Inst, DIBIT, Unit Human Virol, I-20132 Milan, Italy
关键词
CD8(+)CD4(+) T cells; CD8; infection; cytotoxic T lymphocytes;
D O I
10.1073/pnas.95.6.3111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
T cell activation through the T cell receptor is necessary to achieve a specific and effective immune response. We report here that stimulation of CD8(+) T cells through the T cell receptor complex leads to de novo expression of the CD4 antigen on the cell;surface that results in susceptibility of CD8(+) T cells to HIV infection. In addition, activation of peripheral blood mononuclear cells from HIV-infected individuals results in the appearance of double-positive CD4(+)/CD8(+) T cells, which become infected by endogenous HIV. HIV DNA sequences could be detected in uncultured and sorted mature CD3(+)CD8(+) T cells from HIV+ individuals. These results suggest a new mechanism by which HIV could attack the immune system and may help to explain the CD8(+) T cell defects in AIDS patients.
引用
收藏
页码:3111 / 3116
页数:6
相关论文
共 49 条
[1]   EXPRESSION OF CELLULAR GENES IN CD4 POSITIVE LYMPHOID-CELLS INFECTED BY THE HUMAN-IMMUNODEFICIENCY-VIRUS, HIV-1 - EVIDENCE FOR A HOST PROTEIN-SYNTHESIS SHUT-OFF INDUCED BY CELLULAR MESSENGER-RNA DEGRADATION [J].
AGY, MB ;
WAMBACH, M ;
FOY, K ;
KATZE, MG .
VIROLOGY, 1990, 177 (01) :251-258
[2]   CC CKRS: A RANTES, MIP-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophage-tropic HIV-1 [J].
Alkhatib, G ;
Combadiere, C ;
Broder, CC ;
Feng, Y ;
Kennedy, PE ;
Murphy, PM ;
Berger, EA .
SCIENCE, 1996, 272 (5270) :1955-1958
[3]   CD8+ LYMPHOCYTES-T AND PROGRESSION TO AIDS IN HIV-INFECTED MEN - SOME OBSERVATIONS [J].
ANDERSON, RE ;
SHIBOSKI, SC ;
ROYCE, R ;
JEWELL, NP ;
LANG, W ;
WINKELSTEIN, W .
AIDS, 1991, 5 (02) :213-215
[4]   The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes [J].
Bleul, CC ;
Wu, LJ ;
Hoxie, JA ;
Springer, TA ;
Mackay, CR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (05) :1925-1930
[5]  
BLUE ML, 1986, J IMMUNOL, V137, P1202
[6]  
BLUE ML, 1985, J IMMUNOL, V134, P2281
[7]   RECONSTITUTION OF THE SUBCLASS-SPECIFIC EXPRESSION OF CD4 IN THYMOCYTES AND PERIPHERAL T-CELLS OF TRANSGENIC MICE - IDENTIFICATION OF A HUMAN CD4 ENHANCER [J].
BLUM, MD ;
WONG, GT ;
HIGGINS, KM ;
SUNSHINE, MJ ;
LACY, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (05) :1343-1358
[8]   QUANTITATIVE-ANALYSIS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-SPECIFIC CYTOTOXIC LYMPHOCYTE-T (CTL) RESPONSE AT DIFFERENT STAGES OF HIV-1 INFECTION - DIFFERENTIAL CTL RESPONSES TO HIV-1 AND EPSTEIN-BARR-VIRUS IN LATE DISEASE [J].
CARMICHAEL, A ;
JIN, X ;
SISSONS, P ;
BORYSIEWICZ, L .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (02) :249-256
[9]   SYNTHETIC PEPTIDES HOMOLOGOUS TO HIV TRANSMEMBRANE GLYCOPROTEIN SUPPRESS NORMAL HUMAN-LYMPHOCYTE BLASTOGENIC RESPONSE [J].
CHANH, TC ;
KENNEDY, RC ;
KANDA, P .
CELLULAR IMMUNOLOGY, 1988, 111 (01) :77-86
[10]   The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates [J].
Choe, H ;
Farzan, M ;
Sun, Y ;
Sullivan, N ;
Rollins, B ;
Ponath, PD ;
Wu, LJ ;
Mackay, CR ;
LaRosa, G ;
Newman, W ;
Gerard, N ;
Gerard, C ;
Sodroski, J .
CELL, 1996, 85 (07) :1135-1148