Recall response to cytomegalovirus in allograft recipients: mobilization of CD57+, CD28+ cells before expansion of CD57+, CD28- cells within the CD8+ T lymphocyte compartment.

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 CD8 lymphocytosis to plateau at 366 CD57+ CD8+high cells/ mm3 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.