PERIPHERAL T-CELL ACTIVATION IN LONG-TERM RENAL-TRANSPLANT PATIENTS -CONCORDANT UP-REGULATION OF ADHESION MOLECULES AND CYTOKINE GENE-TRANSCRIPTION

In renal transplant patients, the number of T cells expressing high le vels of LFA-1 (LFA-1-bright) and of T cells expressing CD57 increases in response to viral infection, even if the latter is asymptomatic. Th eir role in long-term renal transplant patients with cytomegalovirus ( CMV) antigenemia and concomitant transplant dysfunction was investigat ed. For this purpose, this study used triple-color flow cytometry, flu orescence-activated cell sorting of peripheral blood T cells (CD3+/LFA -1-dim or -bright and CD8+/CD57+ or CD57- subsets), and subsequent sem iquantitative reverse transcription-polymerase chain reaction. Cytokin e mRNA levels for interleukin (IL)-1 beta, IL-2, IL-4, IL-8, IL-10, tu mor necrosis factor alpha, and interferon-gamma, as well as Granzyme A and IL-2R p55 and p75 transcripts were determined and compared in per ipheral blood mononuclear cells and in separated T cell subsets. Altho ugh in patients with CMV infection and/or rejection, cytokine transcri pts were readily detected and the levels in the CD3+/LFA-1-bright subs ets were, by orders of magnitudes, higher than in the LFA-1-dim subset , hardly any cytokine message was found in patients without CMV infect ion or rejection episodes or in control subjects. The expression of Gr anzyme A, which is involved in cytotoxic T lymphocyte-mediated cytotox icity, was not upregulated in LFA-1-bright T cells, which is in discor dance with cytokine levels. Differences between CD57+ and CD57- T cell s were limited to the IL-2R p55 mRNA, of which the former expressed si gnificantly less than the latter. It is concluded that upon virus-indu ced activation of peripheral blood T cells, an effector type that is m arked by high inflammatory but small cytotoxic potential is produced. The results of this study propose that these cells represent a correla te of persistent immune activation and are liable to produce graft dys function, although they are unable to clear the organism from virus in fection because of their lack of cytotoxic potential.