CD8 lymphocytosis in primary cytomegalovirus (CMV) infection of allograft recipients: expansion of an uncommon CD8+ CD57− subset and its progressive replacement by CD8+CD57+ T cells

Abstract

Allograft recipients undergoing cytomegalovirus infection present increased proportions of circulating CD8+ lymphocytes. A longitudinal study of 11 kidney and five liver allograft recipients with primary CMV infection but no other etiological factor of graft dysfunction revealed selective imbalances of peripheral blood CD8+ T cell subsets. Initially, CMV viraemia is associated with elevated CD8+bright T cell numbers and T cell activation. Activation markers fall to normal when viral cultures become negative (before the end of the first month). During the second to sixth month, most (12/16) patients keep up 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 TCR alpha beta+, but were not stained by anti-CD28, CD11b, CD16, CD56, and CD57 antibody. Unexpectedly, CD8+CD57+ T cells, a hallmark of CMV infection, do not appear until the second to sixth month of primary CMV infection, and their numbers increase progressively thereafter. They become the predominant CD8+ T cell subset after 6 months of infection and their persistence for several (up to 4) years is strongly correlated (r = 0.87) with expansion of CD8+ cells. By analysis with MoAbs, there was no bias towards the use of particular TCR-V beta gene families at any time of primary CMV infection. Persistence of CD8 lymphocytosis is thus directly related to the rate of expansion of an uncommon CD8+CD57- subset and its progressive replacement by CD8+CD57+ T cells that are chronically elicited by CMV.

Acute Cytomegalovirus Infection Is Associated with Increased Frequencies of Activated and Apoptosis-Vulnerable T Cells in HIV-1-Infected Infants

“…ϩ T cell activation has been observed in HIVnegative children and transplant recipients with primary CMV infection (18,21,26,29,35). Cellular activation contributes to HIV-1 pathogenesis by a number of mechanisms (reviewed in references 9 and 16), including depletion of T cells via activationinduced cell death (AICD).…”

HCMV microinfections in inflammatory diseases and cancer

“…One specific T-cell population may help us to further understand the role of the virus in these diseases: CD28 − T cells. Early described in CMV-infected patients (Labalette et al, 1994), these cells have been identified in elderly patients, in patients with rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, inflammatory bowel diseases, cardiovascular diseases, chronic rejection, ankylosing spondylitis, and Wegener's granulomatosis (Fasth et al, 2004;Hooper et al, 1999;Lamprecht and Gross, 2007;van Leeuwen et al, 2004).…”

Transient clonal expansion of T-large granular lymphocytes during primary cytomegalovirus infection

“…7 In acute CMV infection in allograft recipients, an initial expansion of a CD8 þ CD57 ÿ T-cell subset has been observed during the first weeks of CMV infection that was progressively replaced by CD8 þ CD57 þ T-cells. 8 Three patients have been reported with CD8 þ CD57 þ T-LGL leukemia after kidney transplantation. Interestingly, two of them have had acute CMV infection a few months before the onset of clonal T-LGL proliferation, suggesting a possible transformation of CMV-induced expansion of T-LGL.…”