In vivo treatment with anti-interleukin-13 antibodies significantly reduces the humoral immune response against an oral immunogen in mice.

Interleukin-13 (IL-13) is a cytokine which significantly enhances the proliferation and differentiation of B lymphocytes. We therefore evaluated its role in the formation of a humoral immune response in vivo. Upon oral immunization with the B subunit of Escherichia coli heat-labile enterotoxin (LT-B), rapid up-regulation of IL-13 mRNA expression in the mesenteric lymph nodes of LT-B intubated mice occurred. This result suggested that IL-13 might be involved in the formation of a mucosal antibody response against LT-B if this cytokine was in fact secreted. To test this possibility, the coding region for murine IL-13 was cloned into the pFLAG-1 expression vector. Recombinant murine IL-13 was purified from bacterial lysates and used as an immunogen to produce polyclonal anti-IL-13 antibodies. Groups of BALB/c mice treated in vivo with anti-IL-13 antibody 2 days before and on the day of oral immunization with LT-B had significantly reduced intestinal IgA and serum IgG and IgA anti-LT-B antibody responses when compared to mice treated with control antibody. Furthermore, groups of mice primed with LT-B and then treated with anti-IL-13 antibody prior to oral immunization with a second dose of LT-B also had significantly reduced intestinal IgA and serum IgG and IgA anti-LT-B antibody titres compared to controls. In vitro LT-B restimulation experiments using splenic mononuclear leucocytes isolated from LT-B primed mice treated with anti-IL-13 antibody demonstrated decreased expression of IL-4 and IL-13 mRNA and decreased IL-4 secretion when compared to controls. Together these results demonstrate an important role for IL-13 in the formation of a humoral immune response at mucosal surfaces.

Local Th1-like responses are induced by intravaginal infection of mice with the mouse pneumonitis biovar of Chlamydia trachomatis.

A critical role for cell-mediated immunity (CMI) has been demonstrated for effecting the resolution of genital infections of mice infected intravaginally with the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn). However, little is known about expression of CMI in the murine genital tract. The mouse MoPn model was used to examine CMI responses in the genital tract and associated lymph nodes during the course of infection. MoPn-specific lymphocytes were present in the genital mucosa, with the maximum level of proliferation in response to MoPn at 3 weeks postinfection. MoPn-stimulated cells secreting gamma interferon were also detected in the cells from the genital mucosa, but few interleukin-4-secreting cells were seen at any time postinfection, indicating the induction of a Th1-like response in the cells of the genital mucosa. The iliac node draining the genital tract was the major node stimulated as a result of a genital infection and exhibited a predominant Th1-like pattern of cytokine secretion as well. Mesenteric lymph node cells demonstrated poor proliferative responses to MoPn and few antigen-stimulated cytokine-secreting cells after the primary infection. However, 7 days after a second infection administered 50 days following the primary infection, there was a marked increase in both proliferative responses and the frequencies of MoPn-stimulated gamma interferon- and interleukin-4-secreting cells. These studies provided information regarding the local CMI response to MoPn in mice which may prove valuable in the development of vaccination strategies for the prevention of chlamydial genital infections.