Mechanisms for induction of acquired host immunity by neutrophil peptide defensins

Human neutrophil peptide (HNP) defensins were studied to determine their po tential effects on adaptive mucosal immunity. Intranasal delivery of HNPs p lus ovalbumin (OVA) enhanced OVA-specific serum IgG antibody (Ab) responses . However, OVA-specific IgA Abs were not induced in mucosal secretions or i n serum. CD4(+) T cells of intranasally immunized mice displayed higher OVA -specific proliferative responses and elevated production of interferon gam ma, interleukin (IL) 5, IL-6, and IL-10 when compared with control groups r eceiving OVA alone. In vitro, HNPs also enhanced both proliferative respons es and T helper (Th) cytokine secretion profiles of CD3 epsilon-stimulated spleen- and Peyer's patch-derived naive CD4(+) T cells. HNPs modulated the expression of costimulatory molecules by lipopolysaccharide- or CD3 epsilon -stimulated splenic and Peyer's patch B or T cell populations, respectively . These studies show that defensins enhance systemic IgG, but not IgA, Ab r esponses through help provided by CD4(+) Th1- and Th2-type cytokines and fo ster B and T cell interactions to link innate immunity with the adaptive im mune system.