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Havenith, S. H. C.; Remmerswaal, E. B. M.; Bemelman, F. J.; Yong, S. L.; van Donselaar‐ van der Pant, K. A. M. I.; van Lier, R. A. W.; ten Berge, I. J. M.
Clinical and experimental immunology, September 2012, Letnik: 169, Številka: 3Journal Article
Summary Rabbit anti‐thymocyte globulin (rATG) induces a long‐lasting lymphocytopenia. CD4+ T cells remain depleted for up to 2 years, whereas the CD8+ T cell compartment is refilled rapidly by highly differentiated CD27‐CD45RA+CD57+effector‐type cells. Because the presence of these highly differentiated CD8+ T cells has been associated with cytomegalovirus (CMV) infection, we questioned to what extent restoration of CMV T cell immunity contributes to the re‐emergence of T cells following rATG treatment. We compared T cell repopulation in six CMV‐seropositive patients with CMV reactivation (reactivating CMV+) to that in three CMV+ patients without reactivation (non‐reactivating CMV+), and to that in three CMV‐seronegative recipients receiving a kidney from a CMV‐seronegative donor (CMV−/−). All patients received rATG because of acute allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus‐specific CD8+ T cells were determined. In reactivating CMV+ patients, total CD8+ T cells reappeared rapidly, whereas in non‐reactivating CMV+ patients they lagged behind. In CMV−/− patients, CD8+ T cell counts had not yet reached pretransplant levels after 2 years. CMV reactivation was indeed followed by a progressive accumulation of CMV‐specific CD8+ T cells. During lymphocytopenia following rATG treatment, serum interleukin (IL)‐7 levels were elevated. Although this was most prominent in the CMV‐seronegative patients, it did not result in an advantage in T cell repopulation in these patients. Repopulated CD8+ T cells showed increased skewing in their Vβ repertoire in both CMV−/− and reactivating CMV‐seropositive patients. We conclude that rapid T cell repopulation following rATG treatment is driven mainly by CMV.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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