IL-4 SECRETION BY CD4(-CELLS INDUCES MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN EARLY LISTERIOSIS() NK1(+) T)

IL-4 is a major promotor of Th2 differentiation and an antagonist of I FN-gamma production. Although experimental listeriosis is characterize d by a Th1 response, IL-4-producing cells were detected in spleens of mice promptly after Listeria monocytogenes infection. We identified th is early IL-4 as inducer of the chemokine, monocyte chemoattractant pr otein-1 (MCP-1), which mainly attracts monocytes/macrophages, but not neutrophils. MCP-l-secreting cells were demonstrable in spleens of mic e infected with L. monocytogenes, and IL-4 neutralization with anti-IL -4 mAb 11B11 markedly diminished frequencies of MCP-1-producing cells. Cell depletion experiments and studies with gene disruption mutant mi ce lacking distinct T cell subsets and surface MHC molecules point to CD4(+)NK1(+) T cells as a cellular source of early IL-4. Since monocyt e infiltration to infective foci contributes to early control of liste riosis, our results suggest that IL-4-producing CD4(+)NK1(+) T cells p articipate in the innate immune response against L. monocytogenes thro ugh MCP-1 induction.