Acute Primary Infection with Cytomegalovirus (CMV) in Kidney Transplant Recipients Results in the Appearance of a Phenotypically Aberrant CD8+ T Cell Population

Human cytomegalovirus (CMV) is a β‐herpesvirus that causes a chronic subclinical infection in healthy man. The immune system is unable to eliminate the virus completely, allowing virus to persist in a latent state. In the immunocompromised host, this equilibrium is disturbed, resulting in a clinical infection. In immunocompromised rats, clinical CMV infection is associated with an increase in NK cells and CD8+ T cells, including a phenotypically aberrant CD8+ T cell population. Using flow cytometry, we examined the effect of acute CMV infection on the composition of leukocyte subsets in immunocompromised patients. Therefore, we used peripheral blood of CMV seronegative patients receiving a kidney from a seronegative (control group) or a seropositive donor. Of the patients receiving a seropositive kidney, only the patients undergoing acute CMV infection were included (experimental group). Special attention was paid to the phenotype of the cytotoxic T cells. The development of acute CMV infection resulted in an increased NK cell number and an activation of both CD4+ and CD8+ T cells, as determined by HLA‐DR expression. An aberrant CD8+ T cell subset with decreased expression of CD8 and TCRαβ appeared in the infected patients. Furthermore, the size of this subpopulation of CD8+ T cells is positively correlated with the viral load.

[1]  M. Smyth,et al.  M144, a Murine Cytomegalovirus (Mcmv)-Encoded Major Histocompatibility Complex Class I Homologue, Confers Tumor Resistance to Natural Killer Cell–Mediated Rejection , 1999, The Journal of experimental medicine.

[2]  P. Fink,et al.  Anergic CD8+ T cells can persist and function in vivo. , 1999, Journal of immunology.

[3]  H. Rollag,et al.  Immunologic parameters as predictive factors of cytomegalovirus disease in renal allograft recipients. , 1999, The Journal of infectious diseases.

[4]  S. Jonjić,et al.  Cytomegaloviral control of MHC class I function in the mouse , 1999, Immunological reviews.

[5]  M. Degli-Esposti,et al.  Cytomegalovirus evasion of natural killer cell responses , 1999, Immunological reviews.

[6]  H. Ploegh Viral strategies of immune evasion. , 1998, Science.

[7]  R. Higgins,et al.  Serial flow cytometric analysis of T-cell surface markers can be useful in differential diagnosis of renal allograft dysfunction. , 1998, Clinical transplantation.

[8]  J. Damoiseaux,et al.  Infection with rat cytomegalovirus (CMV) in the immunocompromised host is associated with the appearance of a T cell population with reduced CD8 and T cell receptor (TCR) expression , 1997, Clinical and experimental immunology.

[9]  H. Vally,et al.  Inhibition of natural killer cells by a cytomegalovirus MHC class I homologue in vivo , 1997, Nature.

[10]  M. Hazzan,et al.  Recall response to cytomegalovirus in allograft recipients: mobilization of CD57+, CD28+ cells before expansion of CD57+, CD28- cells within the CD8+ T lymphocyte compartment. , 1997, Transplantation.

[11]  H. Ploegh,et al.  Viruses use stealth technology to escape from the host immune system. , 1997, Molecular medicine today.

[12]  W. Heath,et al.  Down-modulation of CD8 beta-chain in response to an altered peptide ligand enables developing thymocytes to escape negative selection. , 1997, Cellular immunology.

[13]  P. Price,et al.  Syndromes induced by cytomegalovirus infection. , 1996, Clinical Immunology and Immunopathology.

[14]  R. Schwartz,et al.  Models of T Cell Anergy: Is There a Common Molecular Mechanism? , 1996 .

[15]  N. Sarvetnick,et al.  Sensitization to self (virus) antigen by in situ expression of murine interferon-gamma. , 1995, The Journal of clinical investigation.

[16]  C. Noel,et al.  CD8 lymphocytosis in primary cytomegalovirus (CMV) infection of allograft recipients: expansion of an uncommon CD8+ CD57− subset and its progressive replacement by CD8+CD57+ T cells , 1994, Clinical and experimental immunology.

[17]  M. van der Giessen,et al.  Recovery from cytomegalovirus infection is associated with activation of peripheral blood lymphocytes. , 1992, The Journal of infectious diseases.

[18]  G. Schönrich,et al.  Down-regulation of T cell receptors on self-reactive T cells as a novel mechanism for extrathymic tolerance induction , 1991, Cell.

[19]  W. V. van Son,et al.  Comparison between viremia and antigenemia for detection of cytomegalovirus in blood , 1988, Journal of clinical microbiology.

[20]  S. Beck,et al.  Human cytomegalovirus encodes a glycoprotein homologous to MHC class-I antigens , 1988, Nature.

[21]  B. Sutherland,et al.  Insertion of E. coli photoreactivating enzyme into V79 hamster cells , 1980, Nature.

[22]  C. Bruggeman,et al.  Pathogenicity: animal models. , 1995, Scandinavian journal of infectious diseases. Supplementum.

[23]  D. Bellgrau,et al.  Cytotoxic T-cell precursors with low-level CD8 in the diabetes-prone Biobreeding rat: implications for generation of an autoimmune T-cell repertoire. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[24]  C. V. van Boven,et al.  Biology of rat cytomegalovirus infection. , 1985, Intervirology.