Am J Transplant. 2026 Jan 17:S1600-6135(26)00013-4. doi: 10.1016/j.ajt.2026.01.011. Online ahead of print.
ABSTRACT
Despite booster vaccinations, solid organ transplants (SOT) develop suboptimal immunity and remain at risk of severe COVID-19. Chronic immunosuppression and repeated antigen exposure favors T-cell exhaustion/senescence, potentially challenging development of protective immunity. In a prospective multicenter study including 80 naïve SOT receiving five SARS-CoV-2 mRNA-based vaccine doses, exhausted/senescent T-cell phenotypes were longitudinally profiled at distinct time points and their impact on antigen-specific immune responses was assessed by antibodies, memory B-cells, cytokine-producing T-cells and activation-induced markers on CD4 and CD8 T-cells. We observed wide heterogeneity of vaccine-induced adaptive immunity across compartments. T-cell exhaustion/senescence did not change after three vaccine doses. Notably, high percentages of CD57+, CD57+PD1+, PD1+ and CD57+TIM3+ exhausted/senescent CD4 T-cells at baseline independently predicted poor adaptive functional immune responses despite multiple boosters, regardless of SOT type and immunosuppressive regimen (AUC 0.89, 95%CI 0.81-0.97, sensitivity 0.79, specificity 0.92). Such phenotypes were predominantly observed among tacrolimus/mycophenolate-based regimens. Moreover, SOT with high percentages of CD57+, CD57+PD1+ and CD57+TIM3+ exhausted/senescent CD4 T cells at baseline predicted severe COVID-19 (AUC 0.88, p<0.01). Our study adds preliminary new insight in the field and has clinical implications for risk-stratification against COVID-19 and other viral infections, ultimately guiding decision-making for establishing preventive strategies in SOT patients.
PMID:41554341 | DOI:10.1016/j.ajt.2026.01.011