Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation

Abstract

Background: Deficiencies in cytomegalovirus (CMV)-specific T lymphocytes impair the immunologic response against CMV reactivation after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods: A time-dependent analysis was conducted to determine the association between the percentages and kinetics of interferon-gamma-producing CMV-specific CD4+ and CD8+ T lymphocytes and CMV viremia among 30 allogeneic HSCT recipients.

Results: Higher percentages of CD4+ T lymphocytes activated with CMVpp65 (hazard ratio [HR]: 2.06; 95% confidence interval [95% CI]: 1.18-3.6; P=0.011) and CMV lysate (HR: 1.18; 95% CI: 0.99-1.42; P=0.072), and higher percentages of CD8+ T lymphocytes activated by CMV immediate early-1 (HR: 1.2; 95% CI: 1.01-1.43; P=0.038) and CMVpp65 (HR: 1.12; 95% CI: 1.0-1.27; P=0.060) were associated with time-to-CMV viremia. Furthermore, a higher degree in the decline of CMV lysate-activated CD4+ T lymphocytes (HR: 1.14; 95% CI: 0.96-1.36; P=0.125) and CMVpp65-activated CD8+ T lymphocytes (HR: 1.36; 95% CI: 1.03-1.78; P=0.031) was suggestive of or significantly associated with time-to-CMV viremia.

Conclusions: Higher levels of CMV-specific CD4+ and CD8+ T lymphocytes were associated with subsequent CMV viremia after HSCT. The association between CMV viremia and the degree of decline in CMV-specific T lymphocytes suggests that severe disruption in homeostatic CMV-specific immune environment contributes to the immunopathogenesis of CMV after allogeneic HSCT.