Introduction: Operationally tolerant (TOL) patients display a defect of B cell differentiation, with a deficiency in circulating plasma cells secreting antibodies, which could partly contribute to a pro-tolerogenic environment. Recently described, T follicular helper (Tfh) cells have been reported to play a critical role in B cell differentiation. Methods: We analyzed the frequency and the function of blood Tfh in TOL patients and transplant patients with stable graft function under immunosuppression (STA). Results: We observed a lower proportion of blood Tfh in TOL patients, with a decrease of activated and functional transcriptional and phenotypical subsets. Functionally, Tfh cells from TOL patients failed to induce IgG production by B cells in coculture, which is associated with a significant decrease of IL-21 secretion by Tfh cells. This in vitro defect is linked to a low incidence of post graft DSA immunization, suggesting that the lack of blood Tfh in TOL patients may participate to a pro-tolerogenic environment with reduced risk to develop de novoDSA (dnDSA). This was further demonstrated by an increased proportion of blood Tfh cells in stable transplant patients, with post graft dnDSA immunization. Conclusion: These data provide new insights into the mechanisms of operational tolerance with an impaired function of blood Tfh that could lead to reduce the risk to develop dnDSA and suggest a potential predictive role of blood Tfh on the occurrence of dnDSA in transplant recipients.

CITATION INFORMATION: Danger R, Chenouard A, Chesneau M, Castagnet S, Guérif P, Degauque N, Giral M, Brouard S. Blood Tfh Cells Exhibit Impaired B Cell Help in Operationally Tolerant Patients. Am J Transplant. 2017;17 (suppl 3).

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