The effects of an anti-I-Ab antibody on murine host resistance to Listeria monocytogenes.
Infection with Listeria monocytogenes stimulates T cell proliferation and T cell-derived lymphokine production. The release of lymphokines, in turn, "activates" macrophages, enhancing their bactericidal capacity. Because prior studies suggest that I-A+ accessory cells play a critical role in this pathway, we assessed the effects of an anti-I-A antibody on the murine host resistance to listerial infection. To this end, we infused Listeria into control C57BL/6 mice (I-Ab haplotype) and mice of the same strain which had been pretreated 18 hr earlier with D3137 (a monoclonal IgG2a anti-I-Ab,d antibody). Preliminary studies demonstrated that this antibody can markedly inhibit antigen-induced proliferation of Listeria-dependent T cells in vitro and (at a dose of 1 mg/animal) can markedly reduce I-A expression on splenocytes in vivo. Even though D3137 pretreatment prevented the splenomegaly normally observed after Listeria infusion into mice, it protected animals infused with otherwise lethal concentrations of Listeria. Because antibody-treated animals had sevenfold fewer organisms in their spleens 18 hr after infection and 1000-fold fewer organisms than control animals 3 days after infection, improved survival resulted from an antibody-induced increase in the bactericidal capacity of the MPS. Protection was not noted when C1.18.4 (an IgG2a myeloma protein without known antibody activity) was infused into C57BL/6 mice or when D3137 was infused in B10.BR (I-Ak) mice. D3137 also protected (B10 X B10.BR)F1 mice (which are hybrids bearing I-Ab and I-Ak), suggesting that complete blockade of antigen presentation is not a prerequisite for its protective action. Further studies into the mechanism for these effects may provide new insights into the pathophysiology of MPS activation in response to immunologic challenge.
D000818:Animals; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007113:Immunity, Innate; D007116:Immunization, Passive; D007518:Isoantibodies / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000517:prevention & control; D008222:Lymphokines / Q000378:metabolism; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D008222:Lymphokines