Immunosuppression in solid organ transplant recipients inhibits protective immune responsiveness to pathogens and vaccines. However, specific cell states that associate with failure to generate protective immunity are not known. Here, we perform scRNAseq and CyTOF analyses of PBMC from 12 pediatric solid organ transplant recipients and 8 healthy children revealing the full spectrum of immune cell states present in these individuals, and examine the association of these cell states with the generation of protective humoral and cellular immunity following vaccination. We determined that clonal expansion of a subset of CD8+ effector T cells is significantly increased in immunosuppressed transplant recipients, and that increased frequencies of atypical B cells are associated with impaired humoral but intact T cell responses to vaccination. Interactome analysis suggests that robust cellular interactions between myeloid, T and B cells are required for successful protective immune responses to vaccination in pediatric transplant recipients.

NJC is an employee and shareholder of Quest Diagnostics. All other authors have declared that no conflict of interest exists.

This study was supported by a Clusters of Clinical Research Excellence Award from Boston Children's Hospital to S.B.S, D.M.B, L.S.K and K.D.M..

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The study and protocols were approved by the Institutional Review Board of the Boston Children's Hospital. Written informed consent was received prior to participation.

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