COSTIMULATION OF THE CD3 PATHWAY BY CD28 LIGATION IN HUMAN INTESTINALLYMPHOCYTES

A distinctive characteristic of human intestinal lymphocytes is their low responsiveness to stimuli of the CD3 pathway in vitro. This may be due to anergy resulting from CD3 stimulation without costimulation. C ostimulatory molecules, such as HML-1, VLA-4, CD44, and CD28, may be l acking or unresponsive to ligation. Expression of these costimulatory markers was examined by immunofluorescent staining and how cytometry. Their ability to costimulate intestinal lymphocytes was tested by meas uring changes in proliferation, IL-2 production, and calcium ion mobil ization. HML-1 was found on 87 +/- 8% of intraepithelial lymphocytes b ut only 52 +/- 10% of lamina propria lymphocytes; the density of expre ssion was three times higher on the former. VLA-4 and CD44 were expres sed on more than 80% of both lymphocyte types. CD28 was found on 31 +/ - 26% of intraepithelial lymphocytes and 55 +/- 15% of lamina propria lymphocytes; virtually all CD4(+) T cells and 15 to 26% of CD8(+) T ce lls were CD28(+). Of the four costimulatory molecules, ligation of onl y CD28 increased proliferation and IL-2 production; none affected calc ium ion mobilization with stimulation through the CD3 pathway. The mar ker B7/BB1, a binding partner to CD28, was not present on lymphocytes or epithelial cells by how cytometry. CD28 is the only one of these co stimulatory molecules that enhanced CD3-induced functions of both inte stinal lymphocyte types, but little ligand is available in vivo. Witho ut coligation, CD3 activation may lead to anergy. (C) 1996 Academic Pr ess, Inc.