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Deficiency of cytomegalovirus (CMV)‐specific CD8+ T cells in patients presenting with late‐onset CMV disease several years after transplantation
Author(s) -
Cummins N.W.,
Deziel P.J.,
Abraham R.S.,
Razonable R.R.
Publication year - 2009
Publication title -
transplant infectious disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.69
H-Index - 67
eISSN - 1399-3062
pISSN - 1398-2273
DOI - 10.1111/j.1399-3062.2008.00344.x
Subject(s) - medicine , cytomegalovirus , cytomegalovirus infection , disease , transplantation , cytomegalovirus infections , immunology , cd8 , human cytomegalovirus , virology , virus , herpesviridae , viral disease , immune system
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.