Blocking L-selectin and alpha 4-integrin changes donor cell homing patternand ameliorates murine acute graft versus host disease

L-selectin, LFA-1 and a, integrins play important roles in the homing of na ive T cells into peripheral lymphoid tissues. L-selectin- or LFA-1-deficien t lymphocytes cannot effectively home to lymph nodes (LN), and antibody blo ckade of a, integrins also hinders lymphocytes homing. The present study wa s initiated to explore whether it is feasible to ameliorate acute graft-ver sus-host disease (aGVHD) by modulating the homing process of donor cells in the recipient in a mouse model. Using a fluorescence labeling method, we f ound that two monoclonal antibodies directed at L-selectin and a, integrins , respectively, when used in combination, could delay half of the donor C57 BL/6J mouse spleen cells homing into the LN of recipient BALB/c mouse 15 h after injection. Spleen cells (1 x 10(7)) derived from C57BL/6J (H-2(b)) mi ce were injected into each C.B-17 SCID recipient mouse (H-2(d)) with or wit hout prior incubation with 10 mug each of the two antibodies. T cell repopu lation in the blood was observed in both groups of mice at a comparable lev el 14 days after injection of the donor cells. Eight control mice started t o show aGVHD signs 7-14 days after the injection, and all died by day 31. H owever, among the ten mice that received the antibody-treated donor cells, two died before day 29, four survived between 36 and 78 days, and the remai ning four survived more than 150 days, with two of them aGVHD free. it is a pparent that the temporarily reduced lymphocyte homing into LN reduced the alloreactivity of the donor T cells, thus providing a simple way of modifyi ng aGVHD. This novel approach may shed light on the prevention of aGVHD ass ociated with clinical bone marrow transplantation.