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We have previously shown that 12 days of high‐dose calcineurin inhibition induced tolerance in MHCinbred miniature swine receiving MHC‐mismatched lung, kidney, or co‐transplanted heart/kidney allografts. However, if lung grafts were procured from donation after brain death (DBD), and transplanted alone, they were rejected within 19‐45 days. Here, we investigated whether donor brain death with or without allograft ischemia would also prevent tolerance induction in kidney or heart/kidney recipients. Four kidney recipients treated with 12 days of calcineurin inhibition received organs from donors rendered brain dead for 4 hours. Six heart/kidney recipients also treated with calcineurin inhibition received organs from donors rendered brain dead for 4 hours, 8 hours, or 4 hours with 4 additional hours of cold storage. In contrast to lung allograft recipients, all isolated kidney or heart/kidney recipients that received organs from DBD donors achieved long‐term survival (>100 days) without histologic evidence of rejection. Proinflammatory cytokine gene expression was upregulated in lungs and hearts, but not kidney allografts, after brain death. These data suggest that the deleterious effects of brain death and ischemia on tolerance induction are organ‐specific, which has implications for the application of tolerance to clinical transplantation. Donor brain death prevents tolerance induction in lung, but not isolated kidney or heart plus kidney, allograft recipients, suggesting that the deleterious effects of brain death on tolerance induction are organ specific.

IL‐2 is a known potent T cell growth factor that amplifies lymphocyte responses in vivo. This capacity has led to the use of high‐dose IL‐2 to enhance T cell immunity in patients with AIDS or cancer. However, more recent studies have indicated that IL‐2 is also critical for the development and peripheral expansion of regulatory T cells (Tregs). In the current study, low‐dose IL‐2 (1 million IU/m2BSA/day) was administered to expand Tregs in vivoin naïve nonhuman primates. Our study demonstrated that low‐dose IL‐2 therapy significantly expanded peripheral blood CD4+and CD8+Tregs in vivowith limited expansion of non‐Treg cells. These expanded Tregs are mainly CD45RA−Foxp3 highactivated Tregs and demonstrated potent immunosuppressive function in vitro. The results of this preclinical study can serve as a basis to develop Treg immunotherapy, which has significant therapeutic potential in organ/cellular transplantation.

Viral infections including those due to cytomegalovirus have been associated with accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some animal models. Evidence demonstrating a direct causal relationship between such infections and de novoformation of coronary vascular lesions is lacking. Heterotopic murine cardiac transplants were performed in a parental to F1 combination in animals lacking both T- and B-lymphocytes (RAG??). Coronary vasculopathy developed almost exclusively in the presence of recipient infection with lymphocytic choriomeningitis virus but not in uninfected controls. This process was also dependent upon the presence of natural killer (NK) cells as depletion of NK cells abrogated the process. These data show that a viral infection in its native host, and not previously implicated in the production of CAV, can contribute to the development of advanced coronary vascular lesions in cardiac allotransplants in mice. These data also suggest that virus-induced CAV can develop via an NK-cell-dependent pathway in the absence of T- and B-lymphocytes.

A vertical grating that sinusoidally reverses contrast can be synthesized from two identical component gratings that move with equal velocities in opposite directions (leftward and rightward). Such a counterphase grating is used as a suprathreshold masking pattern. When the mask is of low spatial frequency and is modulated rapidly, a test pattern consisting of an increment of the rightward component and an equivalent simultaneous decrement of the leftward component is highly detectable compared with simultaneous increments or decrements of both components. The visibility of the opponent-movement test signal is strongly facilitated by high-contrast masks. This facilitation is accompanied by a high sensitivity for judging the direction of motion of the test. These results show that certain detection mechanisms are highly sensitive to the difference of the rightward and leftward components. However, when the mask is of threshold contrast, the rightward- and leftward-moving test components appear to be detected independently. A high-contrast grating that rapidly moves in one direction strongly masks gratings moving in the same or opposite direction; this shows that moving patterns are not detected by unidirectional mechanisms when contrast is clearly suprathreshold. The results may be explained by a model with mechanisms that are excited by one direction of motion and inhibited by the opposite direction.