Induction of common mucosal immunity by hormonally immunomodulated peripheral immunization

Abstract

The study described in this report demonstrates that peripheral lymph nodes draining nonmucosal tissues can effectively serve as induction sites for the establishment of common mucosal immunity if the microenvironmental conditions are altered to mimic those normally present within mucosa- associated lymphoid tissues (e.g., Peyer's patches). Lymph nude lymphocytes exposed in situ to the immunomodulatory influences of the hormone 1α,25- dihydroxy vitamin D3 were found to produce less gamma interferon and interleukin-2 (IL-2) and far more IL-4, IL-5, and IL-10 than lymphocytes from control animals. When coupled with vaccination with hepatitis B surface antigen (HBsAg), the hormone-immunomodulated switch from a peripheral lymph node phenotype to a Peyer's patch-like pattern promoted the induction of both a systemic and a common mucosal immune response. This was determined by the observed increased concentrations of serum anti-HBsAg antibody and by finding that anti-HBsAg secretory antibodies were detectable in urogenital, lachrymal, fecal, and oral secretions only in the hormone-treated animals. In addition, specific antibody-secreting cells were detectable in the lamina propria of the lungs and small intestines of the hormone-treated animals subsequent to vaccination, indicating that the homing properties of antigen- specific B cells were being affected by the treatment procedure. The humoral and mucosal immune responses were further augmented if both 1α,25-dihydroxy vitamin D3 and dehydroepiandrosterone were used together as hormonal immunomodulators. This novel immunization technique may afford new opportunities to effectively intervene in sexually transmitted diseases and other diseases caused by mucosal pathogens.