Background: Recent evidence suggests that alloreactive memory T cells are generated by the process of heterologous immunity, whereby memory T cells arising in response to pathogen infection crossreact with donor antigens. Because of their diminished requirements for costimulation during recall, these pathogen-elicited allocrossreactive memory T cells are of particular clinical importance, especially given the emergence of costimulatory blockade as a transplant immunosuppression strategy. Methods: We used an established model of heterologous immunity involving sequential infection of a naïve C57BL/6 recipient with lymphocytic choriomeningitis virus and vaccinia virus, followed by combined skin and bone marrow transplant from a BALB/c donor. Results: We demonstrate that coupling the integrin antagonist anti-leukocyte functional antigen (LFA)-1 with costimulatory blockade could surmount the barrier posed by heterologous immunity in a fully allogeneic murine transplant system. The combined costimulatory and integrin blockade regimen suppressed proliferation of alloreactive memory T cells and attenuated their cytokine effector responses. This combined blockade regimen also promoted the retention of FoxP3 + Tregs in draining lymph nodes. Finally, we show that in an in vitro mixed lymphocyte reaction system using human T cells, the combination of belatacept and anti-LFA-1 was able to suppress cytokine production by alloreactive memory T cells that was resistant to belatacept alone. Conclusions: As an antagonist against human LFA-1 exists and has been used clinically to treat psoriasis, these findings have significant translational potential for future clinical transplant trials. Copyright © 2012 Lippincott Williams & Wilkins.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D−/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016–July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D−/R+ (10 D− were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D− groups (p =.04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p >.05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

Background: Midgut carcinoids are neuroendocrine tumors that commonly metastasize to the intestinal mesentery, where they predispose to intestinal obstruction, ischemia and/or congestion. Because of their location, many mesenteric carcinoid tumors are deemed unresectable due to the risk of uncontrollable bleeding and prolonged intestinal ischemia.Case Presentation: We report the case of a 60-year-old male with a mesenteric carcinoid tumor obstructing his superior mesenteric vein, resulting in intestinal varices and severe recurrent GI bleeds. While his tumor was thought to be unresectable by conventional techniques, it was successfully resected using intestinal autotransplantation to safely gain access to the tumor. This case is the first described application of this technique to carcinoid tumors.Conclusions: Intestinal autotransplantation can be utilized to safely resect mesenteric carcinoid tumors from patients who were not previously thought to be surgical candidates. We review the literature concerning both carcinoid metastases to the intestinal mesentery and the use of intestinal autotransplantation to treat lesions involving the mesenteric root.