ANTIGEN-DRIVEN INDUCTION OF CD11C ON INTESTINAL INTRAEPITHELIAL LYMPHOCYTES AND CD8(-CELLS IN-VIVO() T)

Intraepithelial lymphocytes (IEL) of the intestinal epithelium represe nt a phenotypically and functionally distinct subpopulation of periphe ral T cells. In this study, we report the production of a mAb, designa ted HL3, which exhibits reactivity with a subset of IEL. In differenti al screening assays HL3 reacted with 30 to 50% of IEL, but not with T cells of the thymus, spleen, or lymph nodes. Biochemical characterizat ion revealed that the HL3 mAb recognized p150,95 (CD11c/CD18; CR4), a member of the beta 2-integrin family. Fluorescence flow cytometric ana lyses showed that p150,95 was expressed by TCR-alpha beta or TCR-gamma delta CD4(-)8(+) IEL but not by CD4(+)8(-) IEL. Induction of graft-vs -host (GVH) disease resulted in up-regulation of p150,95 expression on donor-derived CD8(+) T cells in the intestinal epithelium, as well as in the spleen and lymph nodes. GVH also induced MAC-1 (CD11b) express ion on a subset of CD8(+) lymph node T cells, but MAC-1 was not up-reg ulated on CD8(+) IEL in this situation. In contrast, activation of ide ntical T cell responders in vitro resulted in weak induction of p150,9 5 and MAC-1 expression. This result suggested that activation alone wa s insufficient for p150,95 up-regulation and that additional factors a vailable in vivo were essential in this process. In the intestine. ind uction of p150,95 required the presence of intestinal flora as IEL fro m germfree mice lacked p150,95. Interestingly, gamma delta IEL express ing a non-IEL type transgenic TCR were also p150,95(-), but exposure t o Ag in vivo, but not in vitro, resulted in p150,95 induction. This re sult indicated that the constitutive expression of p150,95 on IEL is l ikely due to Ag stimulation via the TCR and not a bystander phenomenon . Overall, the results demonstrated p150,95 to be a hallmark of T cell activation in vivo and an indicator of ongoing antigen-specific T cel l activation in the intestinal epithelium.