Polyclonal T cell depletion with ATG is a common induction therapy in adult and pediatric transplantation. In adults, T cell recovery post-ATG involves homeostatic proliferation of both spared and new thymic emigrant T cells. In infancy, however, HTx pts undergo routine thymectomy, and mechanisms of their immune recovery remain unknown. By systematically analyzing T cell profiles at various timepoints, we determined the impact of ATG on immune reconstitution of thymectomized infant HTx pts. Using blood samples from HTx pts (given at < 1 year of age) who received ATG induction and those who did not, we tracked T cell phenotypes at under 2 years, 2-5 years, and 5-10 years post-transplant. Controls were pts who underwent thymectomy without transplant (Thyx) analyzed at the same timepoints post-surgery and age-matched healthy children (n=3 for each group at each timepoint). T cells were enriched by magnetic negative selection from cryopreserved peripheral mononuclear cells and phenotyped for presence of memory/naïve markers, recent thymic emigrants (RTE), and regulatory T cells (Treg). In Thyx pts, the frequency of CD45RA+RO- naïve T cells was moderately decreased while CD45RA-RO+ memory T cells were moderately increased at all three timepoints. In contrast, ATG induction in HTx pts resulted in profound and persistent reduction of naïve cells and rise of memory cells in the CD4+ T cell population. Additionally, while Thyx pts retained approximately 50% of their CD4+ RTE compared to healthy controls at 2 years post-surgery, only 3% remained in HTx patients with ATG induction. The high frequency of memory CD4+ T cells comprised primarily of CD62Llo effector memory T cells, while neither Thyx nor HTx with ATG treatment altered the frequency of CD62Lhi central memory T cells relative to healthy controls. ATG-treated HTx pts also acquired a persistent CD45RA+RO+ transitional population in CD8+ T cells. Interestingly, although ATG has been reported to spare and induce FoxP3+ Tregs in adults, we did not observe significantly increased Treg frequency in infant HTx pts who received ATG induction. To conclude, in contrast to reports in adults, ATG induction did not increase Tregs in infant HTx pts. Furthermore, ATG induction resulted in a profound and persistent increase in effector memory T cell populations likely due to the lack of thymic output during immune reconstitution.

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