Differential usage of cellular niches by cytomegalovirus versus EBV- and influenza virus-specific CD8+ T cells.
Immunological memory provides long-term protection against reinfection or reactivation of pathogens. Murine memory T cell populations may be compressed following infections with new pathogens. Humans have to retain memory T cells directed against a variety of microbes for many decades. Under these circumstances, the effect of pathogens that mount robust T cell reactivity on the pre-existing memory directed against unrelated microbes is unknown. In this study, we studied peripheral blood memory CD8+ T cells directed against different viruses following primary CMV infection in renal transplant recipients. The entrance of CMV-specific CD8+ T cells expanded the Ag-primed CD8+ T cell compartment rather than competing for space with pre-existing memory T cells specific for persistent or cleared viruses. Neither numbers nor phenotype of EBV- or influenza-specific CD8+ T cells was altered by primary CMV infection. CMV-specific CD8+ T cells accumulated over time, resulting in increased total CD8+ T cell numbers. Additionally, they acquired a highly differentiated cytolytic phenotype that was clearly distinct from EBV- or influenza-reactive T cells. Thus, the human immune system appears to be flexible and is able to expand when encountering CMV. In view of the phenotypic differences between virus-specific T cells, this expansion may take place in cellular niches different from those occupied by EBV- or influenza-specific T cells, thereby preserving immunity to these pathogens.
van Leeuwen
Ester M M
EM
Department of Experimental Immunology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands.
Koning
Jasper J
JJ
Remmerswaal
Ester B M
EB
van Baarle
Debbie
D
van Lier
René A W
RA
ten Berge
Ineke J M
IJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology; D007156:Immunologic Memory; D016030:Kidney Transplantation; D018655:Lymphocyte Count; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000276:immunology; D014780:Viruses / Q000276:immunology*