RECALL RESPONSE TO CYTOMEGALOVIRUS IN ALLOGRAFT RECIPIENTS - MOBILIZATION OF CD57(-)CELLS WITHIN THE CD8(+) T-LYMPHOCYTE COMPARTMENT(), CD28(+) CELLS BEFORE EXPANSION OF CD57(+), CD28()

Background. Strong correlations have been described between persistent ly 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. Meth ods. In a longitudinal study in 123 kidney recipients, we compared 17 primary CMV infections with 27 secondary CMV infections. Subset compos ition of the CD8 compartment was analyzed by flow cytometry. Results. CD8 lymphocytosis occurred significantly earlier (by 17 days on averag e) in CMV reactivations than in primary infections. Both in primary an d secondary infections, CD28(+) CD8(+high) T lymphocytes were mainly r ecruited at the start. In formerly CMV-seropositive patients, preexist ing CD57(+) CD8(+high) T lymphocytes switched at the start from no exp ression of CD28 to high expression of CD28 and, concomitantly, from CD 45RA to high expression of CD45RO. These cells reverted rapidly to a C D28(-) 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 wee ks after the onset of CDS lymphocytosis to plateau at 366 CD57(+) CD8( +high) cells/ mm(3) on average. Conclusions. The faster kinetics of CD 8 lymphocytosis in secondary CMV infection suggests that a recall resp onse triggers cycling ''memory'' cells within the CD28(+) CD8(+high) s ubset, while preexistent CD57(+) CD8(+high) T cells with a long-lived cell phenotype can also be mobilized, possibly through the transient a cquisition of CD28 expression. The protracted accumulation of CD57(+) (and CD28(-)) lymphocytes might then reflect an end-stage differentiat ion.