T-cell Activation and Increased Levels of Cytokines in Children After Liver Transplantation-A Potential Association...

Pediatric liver transplant (LT) recipients are at increased risk of developing a food allergy (liver transplantation-associated food allergy [LTFA]). The underlying immune mechanisms are unknown.

We evaluated the circulating T- and B-cell subsets and serum cytokine profiles of LT recipients with and without LTFA in a cross-sectional cohort study of 43 LT recipients, 8 of whom had LTFA. The T- and B-lymphocyte subsets were analyzed by flow cytometry, and the serum concentrations of 15 cytokines were measured. For comparison, nontransplanted food allergic controls and healthy controls were recruited.

Children with LTFA had increased proportions of newly activated (CD69+) T cells in both CD4+ and CD8+ subsets (P = 0.001 and P < 0.001, respectively), as well as CD4+ T cells of the effector memory CD45RA+ phenotype (P = 0.001), compared with the LT recipients without LTFA. They also had higher serum levels of T helper 2 cytokine interleukin-4 (P = 0.004) and pro-inflammatory cytokines tumor necrosis factor-alpha and tumor necrosis factor-beta (P = 0.007 and P = 0.03, respectively). The corresponding broad immune activation was not noted in the food allergic control group. Notably, the entire cohort of LT recipients exhibited significantly larger proportions of activated, memory, effector, and effector memory CD45RA+ subsets of both CD4+ and CD8+ T cells and higher levels of all the measured cytokines compared with age- and sex-matched healthy control.

An overall immune activation is prevalent in pediatric LT recipients, and especially profound in those with LTFA. Since the food allergic state per se may only partly account for this immune profile, the ongoing immune activation might be associated with the susceptibility to develop LTFA.