Successive emergence of two CD8 subsets in primary CMV infection of allograft recipients.

Abstract

Allograft recipients with cytomegalovirus (CMV) infection develop increased proportions of circulating CD8+ lymphocytes. A longitudinal study of 11 kidney and 5 liver allograft recipients with primary CMV infection but no other aetiological factor to explain graft dysfunction revealed selective imbalances in peripheral blood CD8+ T cell subsets. Initially, CMV viraemia was associated with elevated CD8+bright T cell numbers and T cell activation. Activation markers fell to normal when viral cultures became negative (before the end of the 1st month). During the 2nd-6th months, most (12/16) patients continued to have high CD8+ T cell counts (1050-2900 CD8+ cells/mm3), comprising an uncommon CD8+ T cell subset, as 45-73% of CD8+bright lymphocytes were CD3+ and TCRalphabeta+ but were not stained by anti-CD28, CD11b, CD16, CD56 and CD57 antibody. Unexpectedly, CD8+ CD57+ T cells, a hallmark of CMV infection, did not appear until the 2nd-6th months of primary CMV infection, and their numbers increased progressively thereafter. They became the predominant CD8+ T cell subset after about 6 months of infection and their persistence for several (up to 4) years was strongly correlated (r = 0.87) with expansion of CD8+ cells. Persistence of CD8 lymphocytosis was, thus, directly related to the rate of expansion of an uncommon CD8+ CD57- subset and its progressive replacement by CD8+ CD57+ T cells that were chronically elicited by CMV.