Development of virus-specific CD4+ T cells during primary cytomegalovirus infection

被引:140
作者
Rentenaar, RJ
Gamadia, LE
van der Hoek, N
van Diepen, FNJ
Boom, R
Weel, JFL
Wertheim-van Dillen, PME
van Lier, RAW
ten Berge, IJM
机构
[1] Acad Med Ctr, Renal Transplant Unit F4215, Dept Med, NL-1100 DE Amsterdam, Netherlands
[2] Acad Med Ctr, Dept Immunobiol, Cent Lab, Red Cross Blood Transfus Serv, NL-1100 DE Amsterdam, Netherlands
[3] Acad Med Ctr, Expt & Clin Immunol Lab, NL-1100 DE Amsterdam, Netherlands
[4] Acad Med Ctr, Dept Med, Div Clin Immunol & Rheumatol, NL-1100 DE Amsterdam, Netherlands
关键词
D O I
10.1172/JCI8229
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Although virus-specific CD4(+) T cells have been characterized extensively in latently infected individuals, it is unclear how these protective T-cell responses develop during primary virus infection in humans. Here, we analyzed the kinetics and. characteristics of cytomegalovirus-specific (CMV-specific) CD4(+) T cells in the course of primary CMV infection in kidney transplant recipients. Our data reveal that, as the first sign of specific immunity, circulating CMV-specific CD4(+) T cells become detectable with a median of 7 days after first appearance of CMV-DNA in peripheral blood. These cells produce the T helper 1 type (Th1) cytokines IFN gamma and TNF alpha, but not the T helper 2 type (Th2) cytokine IL4. In primary CMV infection, the vast majority of these circulating virus-specific T cells have features of recently activated naive T cells in that they coexpress CD45RA and CD45R0 and appear to be in the cell cycle. In contrast, in people who have recovered from CMV infection earlier in life, virus-specific T cells do not cycle and express surface markers characteristic of memory T cells. After the initial rise, circulating virus specific CD4(+) T cells decline rapidly. During this phase, a strong rise in IgM and IgG anti-CMV antibody titers occurs, concomitant with the reduction of CMV-DNA in the circulation.
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收藏
页码:541 / 548
页数:8
相关论文
共 30 条
[1]   THE STRUCTURE OF THE MAJOR IMMEDIATE EARLY GENE OF HUMAN CYTOMEGALO-VIRUS STRAIN AD169 [J].
AKRIGG, A ;
WILKINSON, GWG ;
ORAM, JD .
VIRUS RESEARCH, 1985, 2 (02) :107-121
[2]   CD40 LIGAND GENE DEFECTS RESPONSIBLE FOR X-LINKED HYPER-IGM SYNDROME [J].
ALLEN, RC ;
ARMITAGE, RJ ;
CONLEY, ME ;
ROSENBLATT, H ;
JENKINS, NA ;
COPELAND, NG ;
BEDELL, MA ;
EDELHOFF, S ;
DISTECHE, CM ;
SIMONEAUX, DK ;
FANSLOW, WC ;
BELMONT, J ;
SPRIGGS, MK .
SCIENCE, 1993, 259 (5097) :990-993
[3]   MOLECULAR AND BIOLOGICAL CHARACTERIZATION OF A MURINE LIGAND FOR CD40 [J].
ARMITAGE, RJ ;
FANSLOW, WC ;
STROCKBINE, L ;
SATO, TA ;
CLIFFORD, KN ;
MACDUFF, BM ;
ANDERSON, DM ;
GIMPEL, SD ;
DAVISSMITH, T ;
MALISZEWSKI, CR ;
CLARK, EA ;
SMITH, CA ;
GRABSTEIN, KH ;
COSMAN, D ;
SPRIGGS, MK .
NATURE, 1992, 357 (6373) :80-82
[4]  
BAARS PA, 1995, J IMMUNOL, V154, P17
[5]   Helper T cell differentiation is controlled by the cell cycle [J].
Bird, JJ ;
Brown, DR ;
Mullen, AC ;
Moskowitz, NH ;
Mahowald, MA ;
Sider, JR ;
Gajewski, TF ;
Wang, CR ;
Reiner, SL .
IMMUNITY, 1998, 9 (02) :229-237
[6]   A highly sensitive assay for detection and quantitation of human cytomegalovirus DNA in serum and plasma by PCR and electrochemiluminescence [J].
Boom, R ;
Sol, C ;
Gerrits, Y ;
De Boer, M ;
Wertheim-van Dillen, P .
JOURNAL OF CLINICAL MICROBIOLOGY, 1999, 37 (05) :1489-1497
[7]   RAPID AND SIMPLE METHOD FOR PURIFICATION OF NUCLEIC-ACIDS [J].
BOOM, R ;
SOL, CJA ;
SALIMANS, MMM ;
JANSEN, CL ;
WERTHEIMVANDILLEN, PME ;
VANDERNOORDAA, J .
JOURNAL OF CLINICAL MICROBIOLOGY, 1990, 28 (03) :495-503
[8]   Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues [J].
Bucy, RP ;
Hockett, RD ;
Derdeyn, CA ;
Saag, MS ;
Squires, K ;
Sillers, M ;
Mitsuyasu, RT ;
Kilby, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (10) :1391-1398
[9]   THE CD27- SUBSET OF PERIPHERAL-BLOOD MEMORY CD4+ LYMPHOCYTES CONTAINS FUNCTIONALLY DIFFERENTIATED LYMPHOCYTES-T THAT DEVELOP BY PERSISTENT ANTIGENIC-STIMULATION INVIVO [J].
DEJONG, R ;
BROUWER, M ;
HOOIBRINK, B ;
VANDERPOUWKRAAN, T ;
MIEDEMA, F ;
VANLIER, RAW .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (04) :993-999
[10]   CD40 LIGAND MUTATIONS IN X-LINKED IMMUNODEFICIENCY WITH HYPER-IGM [J].
DISANTO, JP ;
BONNEFOY, JY ;
GAUCHAT, JF ;
FISCHER, A ;
DESAINTBASILE, G .
NATURE, 1993, 361 (6412) :541-543