Cellular responses to cytomegalovirus in immunosuppressed patients:: circulating CD8+ T cells recognizing CMVpp65 are present but display functional impairment

被引:56
作者
Engstrand, M
Lidehäll, AK
Tötterman, TH
Herrman, B
Eriksson, BM
Korsgren, O
机构
[1] Univ Hosp, Div Clin Immunol & Transfus Med, SE-75185 Uppsala, Sweden
[2] Univ Hosp, Div Microbiol, SE-75185 Uppsala, Sweden
[3] Univ Hosp, Div Infect Dis, SE-75185 Uppsala, Sweden
关键词
CD8-positive T lymphocytes; CMV; cytomegalovirus; HLA; flow cytometry; MHC;
D O I
10.1046/j.1365-2249.2003.02098.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The availability of tetrameric complexes of HLA class I molecules folded with immunodominant peptides makes it possible to utilize flow cytometry for rapid and highly specific visualization of virus specific CD8(+) T cells. An alternate technique is to incubate whole blood with specific antigens and to subsequently detect and characterize responding T cells (e.g. by performing intracellular staining of interferon-gamma). By using an HLA-A2 tetramer construct folded with the same immunodominant CMV-peptide as that used for peptide pulsing, we monitored both the presence and functional capacity of CMV-specific CD8(+) T cells. In addition T cell activation was assayed by determination of CD38 and CD69 expression. Twelve organ transplant patients and 31 healthy blood donors with latent CMV infection were investigated using CMV pp65 tetramer staining and intracellular staining of interferon-gamma after CMV pp65 peptide pulsing or CMV lysate pulsing. CMV-specific T cells were detected in similar absolute numbers as well as frequencies of T cells in the two groups investigated. However, the CMV-specific CD8(+) T cells in immunosuppressed individuals showed a decreased functional response to the CMV-peptide, as evidenced by reduced interferon-gamma production when compared to healthy blood donors (19%; 42%, P < 0.005). In addition, CD38 expression was markedly higher in immunosuppressed patients compared to healthy blood donors (24%; 6%, P < 0.005). In a case report we demonstrate that reactivation of CMV can occur in an immunosuppressed patient with high number of CMV-specific T cells, but without functional capacity. Hence, these findings reflect impaired activation of cytotoxic T cells controlling latent CMV infection in immunosuppressed patients.
引用
收藏
页码:96 / 104
页数:9
相关论文
共 34 条
[1]   Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants [J].
Aubert, G ;
Hassan-Walker, AF ;
Madrigal, JA ;
Emery, VC ;
Morte, C ;
Grace, S ;
Koh, MBC ;
Potter, M ;
Prentice, HG ;
Dodi, IA ;
Travers, PJ .
JOURNAL OF INFECTIOUS DISEASES, 2001, 184 (08) :955-963
[2]  
Belles-Isles M, 1998, TRANSPLANTATION, V65, P279
[3]   Activated virus-specific T cells are early indicators of anti-CMV immune reactions in liver transplant patients [J].
Benz, C ;
Utermöhlen, O ;
Wulf, A ;
Villmow, B ;
Dries, V ;
Goeser, T ;
Koszinowski, U ;
Busch, DH .
GASTROENTEROLOGY, 2002, 122 (05) :1201-1215
[4]   THE LONG PERSISTENCE OF CMV DNA IN THE BLOOD OF RENAL-TRANSPLANT PATIENTS AFTER RECOVERY FROM CMV INFECTION [J].
BITSCH, A ;
KIRCHNER, H ;
DENNIN, R ;
HOYER, J ;
FRICKE, L ;
STEINHOFF, J ;
SACK, K ;
BEIN, G .
TRANSPLANTATION, 1993, 56 (01) :108-113
[5]   T cell affinity maturation by selective expansion during infection [J].
Busch, DH ;
Pamer, EG .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (04) :701-709
[6]   Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus in vivo [J].
Callan, MFC ;
Tan, L ;
Annels, N ;
Ogg, GS ;
Wilson, JDK ;
O'Callaghan, CA ;
Steven, N ;
McMichael, AJ ;
Rickinson, AB .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (09) :1395-1402
[7]   Characterization of CMVpp65-specific CD8+T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants [J].
Engstrand, M ;
Tournay, C ;
Peyrat, MA ;
Eriksson, BM ;
Wadström, J ;
Wirgart, BZ ;
Romagné, F ;
Bonneville, M ;
Tötterman, TH ;
Korsgren, O .
TRANSPLANTATION, 2000, 69 (11) :2243-2250
[8]   Mycophenolate mofetil - A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation [J].
Fulton, B ;
Markham, A .
DRUGS, 1996, 51 (02) :278-298
[9]   Differentiation of cytomegalovirus-specific CD8+ T cells in healthy and immunosuppressed virus carriers [J].
Gamadia, LE ;
Rentenaar, RJ ;
Baars, PA ;
Remmerswaal, EBM ;
Surachno, S ;
Weel, JFL ;
Toebes, M ;
Schumacher, TNM ;
ten Berge, IJM ;
van Lier, RAW .
BLOOD, 2001, 98 (03) :754-761
[10]   Gamma interferon expression in CD8+ T cells is a marker for circulating cytotoxic T lymphocytes that recognize an HLA A2-restricted epitope of human cytomegalovirus phosphoprotein pp65 [J].
Ghanekar, SA ;
Nomura, LE ;
Suni, MA ;
Picker, LJ ;
Maecker, HT ;
Maino, VC .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 2001, 8 (03) :628-631