Development of CMV‐specific cytotoxic T cells (CMV‐Tc) in pediatric renal transplant recipients with CMV viremia

Abstract

Viral infections are controlled primarily by viral-specific T cells, raising concern for adequate T-cell response to clear CMV infection in transplant recipients receiving lymphocyte-depleting agents (LDA). We examined the rates of CMV viremia and clearance, seroconversion, and CMV-specific CD8+ T cell (CMV-Tc) activity with class of induction agent received. Retrospective review of 45 pediatric renal transplant recipients who received induction with LDA (n=31) or non-LDA (NLDA; n=14) received valganciclovir prophylaxis for 6months post-transplant and CMV-PCR monitoring. CMV-Tc was measured by intracellular IFNγ flow cytometry, when possible, at baseline, 1month after CMV viremia (>5 copies/PCR) and serially until CMV-Tc was positive (≥0.2%). Viremia rates at 1, 2, and 4years post-transplant were higher in LDA vs. NLDA (46.3% vs. 7.2%, 64.2% vs. 7.2%, and 64.2% vs. 7.2%, respectively; p=.002). Viremia rates at these time points in seronegative LDA (50.3%, 71.6%, 71.6%) were significantly or near significantly higher than seronegative NLDA (9.1%, 9.1%, 9.1%; p=.004), seropositive-LDA (22.3%, 22.3%, 22.3%; p=.07), or seropositive NLDA (0%, 0%, 0%; p=.07). Eleven of 17 (64.7%) viremic subjects required valganciclovir dose reduction during the prophylaxis period for leukopenia. All viremic LDA patients developed CMV-Tc. One viremic NLDA patient did not develop CMV-Tc. No patients developed CMV disease. CMV seronegative pediatric renal transplant patients receiving LDA are more likely to have valganciclovir prophylaxis dose reduction and develop subclinical CMV viremia; however, all developed CMV-Tc. Larger prospective studies are needed to further understand the effects of induction agents on CMV-Tc and CMV-Tc's role post-transplant.