IN-VIVO BLOCKING OF L-SELECTIN RESCUES BALB C MICE FROM FATAL LEISHMANIA-MAJOR INFECTION/

Susceptibility and resistance to experimental Leishmania major (L. maj or) infection in mice are associated with a Th2- or Th1-type response, respectively. We have previously shown that immunological events occu rring within the first 24 h after infection in the lymph node (LN) dra ining the site of parasite challenge are critical for the development of either type of T-cell responses. In the present study we manipulate d these events by preventing the entry of naive lymphocytes into the d raining LN by injecting BALB/c mice with a single dose of the anti-L-s electin mAb MEL-14 one day prior to infection with L. major. In contra st to control BALB/c mice, in MEL-14 treated animals the primary lesio n healed 12 weeks after infection. The parasite load in the spleen and lymph nodes of MEL-14 treated mice was significantly reduced. The hea ling was found to be associated with an increased production of IFN-ga mma and with a decrease in IL-4 production by LN cells. We observed a dramatic decrease in cellularity in the draining LN in Mel-14 treated L. major-infected mice within the first week of infection. Moreover, t he cells in the LN of MEL-14 treated mice were highly enriched in acti vated cells as well as in cell influx in the draining LN after local L . major infection of BALB/c mice prevents fatal disease. The data sugg est the MEL-14-induced enrichment of the draining LN in memory and act ivated cells is fundamental for the initiation of a protective Th1-typ e response. (C) 1997 Elsevier Science B.V.