RECALL RESPONSE TO CYTOMEGALOVIRUS IN ALLOGRAFT RECIPIENTS

Abstract

Background. Strong correlations have been described between persistently elevated proportions of CD57(+) (CD28(-)) CD8(+high) T lymphocytes and cytomegalovirus (CMV) infection, in healthy individuals as well as in transplant patients. We investigated whether secondary exposure to CMV triggers recall responses within the CD8 T cell compartment. Methods. In a longitudinal study in 123 kidney recipients, we compared 17 primary CMV infections with 27 secondary CMV infections. Subset composition of the CD8 compartment was analyzed by flow cytometry. Results. CD8 lymphocytosis occurred significantly earlier (by 17 days on average) in CMV reactivations than in primary infections. Both in primary and secondary infections, CD28(+) CD8(+high) T lymphocytes were mainly recruited at the start. In formerly CMV-seropositive patients, preexisting CD57(+) CD8(+high) T lymphocytes switched at the start from no expression of CD28 to high expression of CD28 and, concomitantly, from CD45RA to high expression of CD45RO. These cells reverted rapidly to a CD28(-) and CD45RA(+) phenotype. Nevertheless, the accumulation of CD57(+) (CD28(-)) CD8(+high) T cells was delayed similarly in primary and secondary CMV infection, progressing over a period between 2 and 8 weeks after the onset of CDS lymphocytosis to plateau at 366 CD57(+) CD8(+high) cells/ mm(3) on average. Conclusions. The faster kinetics of CD8 lymphocytosis in secondary CMV infection suggests that a recall response triggers cycling ''memory'' cells within the CD28(+) CD8(+high) subset, while preexistent CD57(+) CD8(+high) T cells with a long-lived cell phenotype can also be mobilized, possibly through the transient acquisition of CD28 expression. The protracted accumulation of CD57(+) (and CD28(-)) lymphocytes might then reflect an end-stage differentiation.