MODULATION OF LYMPHOCYTE INTERACTION WITH ENDOTHELIUM AND HOMING BY HIV-1 GP120

We have previously shown that HIV-1 glycoprotein 120(gp120) induces CD 4 association with several molecules on the surface of CD4(+) lymphocy tes. Since one of these molecules was CD38, involved in lymphocyte/end othelium interaction, this article examines the possibility that gp120 /CD4 binding alters CD4(+) T cell interaction with vascular endotheliu m in vitro and in vivo. Cocapping experiments showed that gp120 induce d CD4 association with CD38, CD29, CD49d, and CD11a in peripheral bloo d CD4(+) T cells. Two in vitro binding assays were used to evaluate th e effect of gp120. A static binding assay, performed at 37 degrees C, evaluated stable interactions mediated by integrins, and a dynamic bin ding assay, performed at 4 degrees C on a rocking shelf, evaluated wea k interactions mediated by constitutively active molecules such as sel ectins and CD38. Gp120 increased dynamic binding and inhibited static binding to the endothelium of peripheral blood CD4(+) T cells and SUPT -1 cells. Binding inhibition with mAbs suggested that the gp120 effect on dynamic binding involved CD38, CD31, and CD49d, whereas the effect on static binding involved CD11a and CD49d. In vivo experiments showe d that treatment of 2D4 cells, a CD4(-)CD8(-) mouse T cell clone trans fected with the human CD4, with gp120 increased their homing into the spleen, intestine, and mesenteric lymph nodes, whereas it decreased ho ming into peripheral lymph nodes. Alteration of lymphocyte homing may contribute to immune deficiency in HIV-lf patients by decreasing the p robability of an encounter between Ags and lymphocytes and inhibiting the spread of effector lymphocytes into tissues.