Abstract

Drug-based immunosuppression significantly increases the risk of infection and cancer. Development of new approaches to minimize or eliminate graft rejection is of great interest to the transplant community. Establishment of durable hematopoietic chimerism through hematopoietic stem cell transplantation (HSCT) has been shown in preclinical models and patients to lead to donor specific tolerance. Those chimeric patients immune competence to virus infection never been investigated. Herein, we investigated the recall immune responses in a series of chimeric renal transplant recipients received CD8+/TCR- facilitating cell-based hematopoietic stem cell transplant (termed FCRx) to induce tolerance to mismatched renal allografts. This study took advantage of recent breakthroughs in the single-cell quantification of human peripheral blood B-cell responses to prospectively evaluate both B- and T-cell responses to the seasonal influenza vaccine (A/California[H1N1], A/SWIZERLAND [H3N2], B/BRISBANE, B/PHUKET] at day 0 before vaccination and day 30 post vaccination in 3 chimeric renal transplant recipients (proved by HLA PCR], and 3 healthy controls. Utilizing ELISA, flowcytometry analysis of T & B phenotypes, intracellular IFN-Y, B-cell culture supernatant and haemaggultination inhibition assay. there was a significant overall B-cell response to influenza vaccination, quantified by the frequency of influenza-specific antibody-secreting cells (ASC) in peripheral blood of chimeric patients but the magnitude was significantly reduced compared to healthy controls. The magnitude of the sero-response and the rate of sero-conversion were also blunted. The influenza-specific interferon-gamma (IFNγ) T-cell response was significantly reduced in transplant recipients; however, there was no correlation between the magnitude of the influenza specific IgG ASC, IFNγ responses and HIA. The induction of memory T- and B-cell responses to influenza vaccination supports the recommendation to vaccinate while the blunted responses in chimeric transplant patients.

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