CONTROL OF LEISHMANIA-MAJOR INFECTION IN BALB C MICE BY INHIBITION OFEARLY LYMPHOCYTE ENTRY INTO PERIPHERAL LYMPH-NODES/

A single i.p. injection with the anti-CD62L (anti-L-selectin) mAb Mel- 14 before parasite challenge protected BALB/c mice from the otherwise lethal infection with Leishmania major. The Mel-14 mAb treatment resul ted in a significant (>90%) decrease in cellularity of the popliteal l ymph node (PLN) with a decrease in the proportion of CD4(+) cells and an increase of the proportion of B220(+) cells. Furthermore, both acti vated cells (CD25(+) and CD69(+)) and cells of the memory phenotype (C D45RB(dull) CD44(high)) were significantly enriched in PLN from Mel-14 -treated BALB/c mice. After infection with L. major, the otherwise mas sive cellular infiltration in the draining PLN was completely blocked in the Mel-14-treated mice, and in these;animals the high representati on of both activated and memory cells in PLN remained characteristic f or the first days of infection. The protective effect was found to be associated with a markedly increased production of IFN-gamma and with a decrease in IL-4 production upon restimulation of PLN and spleen cel ls with L. major Ag in vitro. The cured mice were found to be resistan t against a secondary challenge with the parasites. These data suggest that the induction of a nonprotective Th2 response to L. major is ass ociated with the entry of lymphocytes from the recirculating pool into the draining LN. The Mel-14-induced changes in the lymphoid microenvi ronment of the draining peripheral LN appear to favor the development of a protective Th1 cell-mediated immune response against the parasite .