Dynamics of cytokine expression in HIV productively infected primary CD4+ T cells

被引:29
作者
Bahbouhi, B [1 ]
Landay, A [1 ]
Al-Harthi, L [1 ]
机构
[1] Rush Univ, Ctr Med, Dept Immunol Microbiol, Chicago, IL 60612 USA
关键词
D O I
10.1182/blood-2003-12-4172
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Using intracellular p24 staining to discriminate between bystander and HIV productively infected cells, we evaluated the properties of HIV productively infected cells in terms of cytokine expression, activation status, apoptosis, and cell proliferation. We demonstrate that HIV productively infected primary CD4(+) T cells express 12- to 47-fold higher type 1 cytokines than bystander or mock-infected cells. The frequency of HIV productive replication occurred predominantly in T-helper 1 (Th1), followed by Th0, then by Th2 cells. These productively infected cells expressed elevated levels of CD95, CD25, CXC chemokine receptor 4 (CXCR4), and CC chemokine receptor 5 (CCR5). While productively infected cells wore only 1.8-fold higher in apoptosis frequency, they up-regulated the antiapoptotic protein B-cell leukemia 2 (Bcl-2) by 10-fold. Up-regulation of interieukin-2 (IL-2) and Bcl-2 were dependent on phosphatidylinositol-3-kinase signal transduction, given that it was down-regulated by Wortmanin treatment. Additionally, 60% of productively infected cells entered the cell cycle, as evaluated by Ki67 staining, but none divided, as evaluated by carboxyfluoresccin diacetate succinimidylester (CFSE) staining. Evaluation of cell cycle progression by costaining for DNA and RNA indicated that the cells were arrested in G(2)/M. Collectively, these data indicate that HIV replication occurs predominantly in Th1 cells and is associated with immune activation and up-regulation of Bcl-2, conferring a considerable degree of protection against apoptosis in the productively infected subpopulation.
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页码:4581 / 4587
页数:7
相关论文
共 50 条
[1]  
Adachi Y, 1996, J IMMUNOL, V157, P4184
[2]   Induction of HIV-1 replication by type I-like cytokines, interleukin (IL)-12 and IL-15: Effect on viral transcriptional activation, cellular proliferation, and endogenous cytokine production [J].
Al-Harthi, L ;
Roebuck, KA ;
Landay, A .
JOURNAL OF CLINICAL IMMUNOLOGY, 1998, 18 (02) :124-131
[3]   Maximum suppression of HIV replication leads to the restoration of HIV-specific responses in early HIV disease [J].
Al-Harthi, L ;
Siegel, J ;
Spritzler, J ;
Pottage, J ;
Agnoli, M ;
Landay, A .
AIDS, 2000, 14 (07) :761-770
[4]   Could Nef and Vpr proteins contribute to disease progression by promoting depletion of bystander cells and prolonged survival of HIV-infected cells? [J].
Azad, AA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 267 (03) :677-685
[5]   HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes:: involvement of protein kinase C-βII and -δ [J].
Bennasser, Y ;
Bahraoui, E .
FASEB JOURNAL, 2002, 16 (06) :546-554
[6]   Death of CD4+ T-cell lines caused by human immunodeficiency virus type 1 does not depend on caspases or apoptosis [J].
Bolton, DL ;
Hahn, BI ;
Park, EA ;
Lehnhoff, LL ;
Hornung, F ;
Lenardo, MJ .
JOURNAL OF VIROLOGY, 2002, 76 (10) :5094-5107
[7]   EFFECTS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT PROTEIN ON THE EXPRESSION OF INFLAMMATORY CYTOKINES [J].
BUONAGURO, L ;
BARILLARI, G ;
CHANG, HK ;
BOHAN, CA ;
KAO, V ;
MORGAN, R ;
GALLO, RC ;
ENSOLI, B .
JOURNAL OF VIROLOGY, 1992, 66 (12) :7159-7167
[8]   CHANGES IN INTERLEUKIN-2 AND INTERLEUKIN-4 PRODUCTION IN ASYMPTOMATIC, HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE INDIVIDUALS [J].
CLERICI, M ;
HAKIM, FT ;
VENZON, DJ ;
BLATT, S ;
HENDRIX, CW ;
WYNN, TA ;
SHEARER, GM .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (03) :759-765
[9]   Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4+ T lymphocytes [J].
Ebert, LM ;
McColl, SR .
JOURNAL OF IMMUNOLOGY, 2002, 168 (01) :65-72
[10]  
Ehret A, 2001, EUR J IMMUNOL, V31, P1790, DOI 10.1002/1521-4141(200106)31:6<1790::AID-IMMU1790>3.0.CO