title: Deficiency of cytomegalovirus (CMV)-specific CD8+ T cells in patients presenting with late-onset CMV disease several years after transplantation.
abstract: Cytomegalovirus (CMV) is a major cause of morbidity and mortality among transplant recipients. The routine use of anti-CMV prophylaxis has modified the epidemiology of post-transplant CMV infection by delaying the onset of clinical disease. While the majority of delayed-onset CMV disease still occurs during the first year after transplant, reports of late-onset CMV disease presenting many years after transplantation are increasing. Here, we describe 2 CMV-seropositive transplant recipients who presented with late-onset CMV disease at 8 and 11 years after transplantation. To determine whether CMV disease occurring at a very late period after transplantation is related to immune competence, we assessed global and CMV-specific cellular immunity by evaluating the activation capability of CD8+ T cells to a mitogenic stimulus and by quantitative and functional analysis (as assessed by intracellular cytokine production and degranulation) of CMV-specific CD8+ T cells. In both patients, we demonstrated the absence or marked deficiency of CMV-specific T-cell immunity despite CMV seropositivity, and in one patient, a partial defect in the immune response to phorbol myristate acetate and ionomycin suggesting impaired global immune competence. Hence, our data suggest that late-onset CMV disease occurring many years after transplantation remains related to defects in the immune competence of patients. Measurement of CMV-specific cellular immune competence may therefore provide an additional tool to screen for patients at high risk of developing late-onset CMV disease. The clinical utility of this assay, however, will need to be evaluated in larger prospective studies.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: N W
authors.initials: NW
authors.lastname: Cummins
authors.forename: P J
authors.initials: PJ
authors.lastname: Deziel
authors.forename: R S
authors.initials: RS
authors.lastname: Abraham
authors.forename: R R
authors.initials: RR
authors.lastname: Razonable
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016030:Kidney Transplantation / Q000009:adverse effects*; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology; D008297:Male; D016035:Pancreas Transplantation / Q000009:adverse effects*; D013997:Time Factors