FUNCTIONAL-CHANGES OF INTESTINAL INTRAEPITHELIAL LYMPHOCYTES DURING ACUTE GRAFT-VERSUS-HOST DISEASE - CORRELATION WITH PHENOTYPE

While the pathological characteristics of acute graft versus host dise ase (GvHD) have been defined for many target organs, little attention has been paid to the functional changes of lymphocytes in target organ s such as the liver and small intestine, We have shown previously, uti lizing a nonlethal parent (C57BL/6J) into the F-1 (C57BL/6J x DBA2J F- 1) GvHD model, that the intestinal mucosa is infiltrated exclusively b y donor T cells with a CD8(+) phenotype during the first 3 weeks post- GvHD induction, The present study investigated the functional changes associated with the phenotypic changes of intestinal intraepithelial l ymphocytes (IEL) during the acute phase of GvHD, IEL displayed specifi c anti-host cytolytic activity during the second and third week after GvHD induction, In addition, enhanced cytolytic activity, detected in the presence of anti-CD3 antibody, was apparent during the second thro ugh fourth week, with a peak in the third week after GvHD induction, T he IEL also showed enhanced proliferative responses to immobilized ant i-CDS during the first 2 weeks of acute GvHD, while profound inhibitio n of proliferation was observed in the splenocyte population of the sa me animals, During weeks 2 and 3 post-GvHD induction, the V-beta distr ibution of host IEL remained unchanged while the V-beta distribution o f infiltrating donor CD8(+) cells resembled that of the donor IEL popu lation, In the small intestine, the increased cytolytic and proliferat ive activity of IEL during the course of the disease may provide a rat ionale for the involvement of this organ in the pathology associated w ith GvHD.