T cell depletion is commonly used in organ transplantation for immunosuppression; however, a restoration of T cell homeostasis following depletion leads to increased memory T cells, which may promote transplant rejection. The cytokine IL-7 is important for controlling lymphopoiesis under both normal and lymphopenic conditions. Here, we investigated whether blocking IL-7 signaling with a mAb that targets IL-7 receptor α (IL-7Rα) alone or following T cell depletion confers an advantage for allograft survival in murine transplant models. We found that IL-7R blockade alone induced indefinite pancreatic islet allograft survival if anti-IL-7R treatment was started 3 weeks before graft. IL-7R blockade following anti-CD4-and anti-CD8-mediated T cell depletion markedly prolonged skin allograft survival. Furthermore, IL-7 inhibition in combination with T cell depletion synergized with either CTLA-4Ig administration or suboptimal doses of tacrolimus to induce long-term skin graft acceptance in this stringent transplant model. Together, these therapies inhibited T cell reconstitution, decreased memory T cell numbers, increased the relative frequency of Tregs, and abrogated both cellular and humoral alloimmune responses. Our data suggest that IL-7R blockade following T cell depletion has potential as a robust, immunosuppressive therapy in transplantation.
There is no recommendation regarding the timing for implant surgery in patients with head and neck cancer (HNC) who require postoperative radiation therapy (RT). This systematic review focused on the literature about the outcomes of implants placed during ablative surgery in patients with HNC who underwent postoperative RT. Implants placed after radiation therapy and implants placed in reconstructed jaws were excluded. Four comparative studies involving 755 native mandible primary implants were analyzed. The survival rate with postimplantation RT was 89.6% vs 98.6% in patients with no additional radiation. The overall success of implant‐retained overdenture in patients with RT performed postimplantation was 67.4% vs 93.1% in patients with implant surgery that was carried out 1 year after the completion of radiation therapy. Only five cases of osteoradionecrosis (ORN) of the jaw were reported. The outcomes for implant survival rates appear to be positive for irradiated implants.
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