HIV-1 transgenic rats develop T cell abnormalities

被引:34
作者
Reid, W
Abdelwahab, S
Sadowska, M
Huso, D
Neal, A
Ahearn, A
Bryant, J
Gallo, RC
Lewis, GK
Reitz, M
机构
[1] Univ Maryland, Inst Human Virol, Div Basic Sci, Baltimore, MD 21201 USA
[2] Univ Maryland, Div Vaccine Res, Baltimore, MD 21201 USA
[3] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
[4] Johns Hopkins Univ, Sch Med, Div Comparat Med, Baltimore, MD 21205 USA
[5] Univ Maryland, Mol & Cellular Biol Program, Baltimore, MD 21201 USA
[6] Univ Maryland, Inst Human Virol, Anim Model Div, Baltimore, MD 21201 USA
关键词
Th1/Th2; cells; HIV-1; transgenic;
D O I
10.1016/j.virol.2003.12.010
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4(+) and CD8(+) T cells able to produce IFN-gamma following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4(+) and CD8(+) effector/memory (CD45RC(-)CD62L(-)) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naive (CD45RC(+)CD62L(+)) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:111 / 119
页数:9
相关论文
共 32 条
[1]   Immunological memory and protective immunity: Understanding their relation [J].
Ahmed, R ;
Gray, D .
SCIENCE, 1996, 272 (5258) :54-60
[2]   IMMUNOGLOBULIN-V(H)3 GENE-PRODUCTS - NATURAL LIGANDS FOR HIV GP120 [J].
BERBERIAN, L ;
GOODGLICK, L ;
KIPPS, TJ ;
BRAUN, J .
SCIENCE, 1993, 261 (5128) :1588-1591
[3]   A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory [J].
Bourgeois, C ;
Rocha, B ;
Tanchot, C .
SCIENCE, 2002, 297 (5589) :2060-2063
[4]  
CARTER LL, 1995, J IMMUNOL, V155, P1028
[5]  
COHEN OR, AIDS VACCINE RES, P11
[6]   Evidence for increased T cell turnover and decreased thymic output in HIV infection [J].
Douek, DC ;
Betts, MR ;
Hill, BJ ;
Little, SJ ;
Lempicki, R ;
Metcalf, JA ;
Casazza, J ;
Yoder, C ;
Adelsberger, JW ;
Stevens, RA ;
Baseler, MW ;
Keiser, P ;
Richman, DD ;
Davey, RT ;
Koup, RA .
JOURNAL OF IMMUNOLOGY, 2001, 167 (11) :6663-6668
[7]   T cell fitness determined by signal strength [J].
Gett, AV ;
Sallusto, F ;
Lanzavecchia, A ;
Geginat, J .
NATURE IMMUNOLOGY, 2003, 4 (04) :355-360
[8]   ACTIVATION-INDUCED DEATH BY APOPTOSIS IN CD4+ T-CELLS FROM HUMAN-IMMUNODEFICIENCY-VIRUS INFECTED ASYMPTOMATIC INDIVIDUALS [J].
GROUX, H ;
TORPIER, G ;
MONTE, D ;
MOUTON, Y ;
CAPRON, A ;
AMEISEN, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 175 (02) :331-340
[9]   The pathogenicity of human immunodeficiency virus (HIV) type 1 Nef in CD4C/HIV transgenic mice is abolished by mutation of its SH3-binding domain, and disease development is delayed in the absence of Hck [J].
Hanna, Z ;
Weng, XD ;
Kay, DG ;
Poudrier, J ;
Lowell, C ;
Jolicoeur, P .
JOURNAL OF VIROLOGY, 2001, 75 (19) :9378-9392
[10]   Single expression of CD45RC and RT6 in correlation with T-helper 1 and T-helper 2 cytokine patterns in the rat [J].
Hylkema, MN ;
van der Deen, M ;
Pater, JM ;
Kampinga, J ;
Nieuwenhuis, P ;
Groen, H .
CELLULAR IMMUNOLOGY, 2000, 199 (02) :89-96