Secondhand Smoke Shortens Transplant Survival in Mice

Research unveils novel immunologic mechanism behind smoke-related allograft rejection

THURSDAY, March 1 (HealthDay News) -- The immunologic mechanisms behind smoke-related graft rejection have been elucidated, according to a study published in the March issue of the American Journal of Transplantation.

F. Wan, of the University of Texas Health Science Center in Tyler, and colleagues used mouse transplant models to investigate the impact of exposure to smoke on transplant survival and its mechanism of action.

The researchers found that secondhand smoke (SHS) impaired long-term islet allograft survival induced by CD154 costimulatory blockade plus donor-specific splenocyte transfusion (DST). SHS did not alter acute islet allograft rejection, nor did it directly interfere with vigorously alloreactive T-cell proliferation in vivo and in vitro. SHS did not cause a significant reduction in either naturally occurring or induced CD4+CD25+ regulatory T cell numbers. However, SHS suppressed mRNA and protein expression of indoleamine 2, 3-dioxygenase (IDO) and its activity upon transplantation. Overexpression of IDO in islet allografts restored their long-term survival induced by CD154 blockade.

"Our study for the first time demonstrates that SHS shortens allograft survival in a cause-effect manner and unveils a novel immunologic mechanism underlying smoking-related allograft rejection," the authors write.

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