Prolonged Hya‐Disparate Skin Graft Survival in Ethanol‐Consuming Mice: Correlation With Impaired Delayed Hypersensitivity

Abstract

Background: Ethanol consumption impairs cell‐mediated immunity and enhances humoral immunity. Among cell‐mediated immune reactions, little is known of the effect of ethanol on chronic graft rejection. Allograft responses against the male‐specific minor histocompatibility antigen, Hya, are widely used to study chronic graft rejection.Methods: Female C57BL/6 (B6) mice were fed ethanol‐containing liquid diets, were pair‐fed an isocaloric liquid control diet, or were fed solid diet and water ad libitum. One week after diet initiation, the mice were grafted with split thickness, orthotopic male tail skin grafts, and the integrity of the grafts was monitored as the diet continued. Delayed hypersensitivity (DTH) was also determined in these same mice. In addition, Hya‐cytolytic T‐cell–deficient syngeneic major histocompatibility complex mutant B6.C‐H2bm13 (bm13) and B6.C‐H2bm14 (bm14) mice were assessed for skin graft rejection, DTH, and cytotoxic T‐lymphocyte (CTL) activity.Results: Ethanol‐consuming female B6 mice are impaired in their ability to reject syngeneic male skin grafts and to develop Hya‐specific DTH responses. To address the underlying mechanism, we show that Hya graft rejection correlates with DTH and not with CTL activity. Female B6 mice clearly differ from female bm13 and bm14 mice in their ability to generate CTLs against Hya antigen. Despite their inability to make Hya‐specific CTL responses, bm13 and bm14 female mice, nevertheless, make Hya‐specific DTH responses and ultimately reject Hya‐disparate skin grafts, indicating that Hya‐specific graft rejection results from DTH. Ethanol, by impairing Hya‐specific DTH, inhibits Hya‐specific skin graft rejection.Conclusions: We demonstrate that ethanol consumption impairs Hya‐specific graft rejection. In addition, experiments with mice unable to generate anti‐Hya CTLs support previous observations suggesting that DTH responses are sufficient to cause rejection of Hya‐incompatible grafts.