An immunomodulatory function for neutrophils during the induction of a CD4(+) Th2 response in BALB/c mice infected with Leishmania major

The possible immunomodulatory role of polymorphonuclear leukocytes (PMN) in CD4(+) T lymphocyte differentiation in mice was examined by studying the e ffect of transient depletion of PMN during the early phase after Leishmania major delivery. A single injection of the PMN-depleting NIMP-R14 mAb 6 h b efore infection with L. major prevented the early burst of IL-4 mRNA transc ription otherwise occurring in the draining lymph node of susceptible BALB/ c mice. Since this early burst of IL-4 mRNA transcripts had previously been shown to instruct Th2 differentiation in mice from this strain, we examine d the effect of PMN depletion on Th subset differentiation at later time po ints after infection, The transient depletion of PR IN in BALB/c mice was s ufficient to inhibit Th2 cell development otherwise occurring after L. majo r infection. Decreased Th2 responses were paralleled with partial resolutio n of the footpad lesions induced by L. major. Furthermore, draining lymph n ode-derived CD4(+) T cells from PMN-depleted mice remained responsive to IL -12 after L. major infection, unlike those of infected BALB/c mice receivin g control Ab, PMN depletion had no effect when the NIMP-R14 mAb was injecte d 24 h postinfection. The protective effect of PMN depletion was shown to b e IL-12 dependent, as concomitant neutralization of IL-12 reversed the prot ective effect of PMN depletion, These results suggest a role for an early w ave of PMN in the development of the Th2 response characteristic of mice su sceptible to infection with L. major.