Eosinophils restrain humoral alloimmunity after lung transplantation.

While the function of many leukocytes in transplant biology has been well defined, the role of eosinophils is controversial and remains poorly explored. Conflicting data exist regarding eosinophils' role in alloimmunity. Due to their prevalence in the lung, and their defined role in other pulmonary pathologies such as asthma, we set out to explore the role of eosinophils in the long-term maintenance of the lung allograft. We noted that depletion of eosinophils results in the generation of donor-specific antibodies. Eosinophil depletion increased memory B cell, plasma cell, and antibody-secreting cell differentiation and resulted in de novo generation of follicular germinal centers. Germinal center formation depended on the expansion of CD4+Foxp3-Bcl6+CXCR5+PD-1+ T follicular helper (Tfh) cells, which increase in number after eosinophil depletion. Mechanistically, we demonstrate that eosinophils prevent Tfh cell generation by acting as the dominant source of IFN-γ in an established lung allograft, thus facilitating Th1 rather than Tfh polarization of naive CD4+ T cells. Our data thus describe what we believe is a unique and previously unknown role for eosinophils in maintaining allograft tolerance and suggest that indiscriminate administration of eosinophil-lytic corticosteroids for treatment of acute cellular rejection may inadvertently promote humoral alloimmunity.

Current Developments in the Preclinical and Clinical use of Natural Killer T cells.

Natural killer T (NKT) cells play a pivotal role as a bridge between the innate and the adaptive immune response and are instrumental in the regulation of homeostasis. In this review, we discuss the potential for NKT cells to serve as biodrugs in viral infections and in cancer. NKT cells are being investigated for their use as a prognostic biomarker, an immune adjuvant, and as a form of cellular therapy. Historically, the clinical utility of NKT cells was hampered by their low frequency in the blood, discrepancies in nomenclature, and challenges with ex vivo expansion. However, recent advances in the field have permitted the development of several NKT cell-based preclinical and clinical strategies. These new developments pave the way for the successful implementation of NKT cell-based approaches for the treatment of human disease.