Comparison of retinoic acid (oral and subcutaneous) and vitamin A (oral) effects on immune response in vitamin A deficient mice

Open Access
- Author:
- Zhou, Hanbing
- Graduate Program:
- Immunology and Infectious Diseases
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- November 08, 2012
- Committee Members:
- A Catharine Ross, Thesis Advisor/Co-Advisor
Margherita Teresa Anna Cantorna, Thesis Advisor/Co-Advisor
Na Xiong, Thesis Advisor/Co-Advisor - Keywords:
- vitamin A
retinoic acid
mucosal immunity
IgA - Abstract:
- Vitamin A deficiency is widely present in developing countries, affecting human’s health especially children with high morbidity and mortality. Vitamin A deficient (VAD) animals have the impaired immunity to many infections. In vaccines models VAD animals show depressed antibody and cytokine production, reduced cytotoxic T lymphocyte activity and impaired T lymphocytes trafficking to the gastrointestinal tract. Vitamin A (VA) supplements have been shown to play an important role in reducing mortality, improving recovery from measles, and decreasing the severity of malaria infection in children. Oral VA supplementation as well as retinoic acid (RA) administration restores the impaired mucosal immune response and vaccine efficiency in VAD mice model. RA subcutaneous (sc) injection has been shown to induce the homing of T and B cells to the gut and to stimulate immunoglobulin A (IgA)+ plasma cells generation. Ovalbumin (OVA) is a widely used oral antigen for immune and oral tolerance studies. Tetanus toxoid (TT) is a protein antigen used as a vaccine against tetanus, to prevent the infection of Clostridium tetani. Cholera Toxin Subunit B (CTB), as a possible nontoxic adjuvant shown in animal studies, was mixed with OVA as a mucosal adjuvant in my project. Here, we compared the different supplementation (VA orally versus RA orally or by subcutaneous injection) in the VAD mice model, with OVA and TT as antigens delivered through oral challenge or subcutaneous injection. RA sc supplementation enhanced the plasma and fecal OVA specific IgA and TT specific IgG production in secondary immune response and plasma OVA specific IgA after third immunization. RA oral supplementation only showed its effect on increasing plasma OVA specific IgA response after the third immunization. Whereas VA supplementation did not affect the OVA mucosal immunization, it only strengthens TT specific IgG response after the secondary immunization. From these results, RA, especially the RA sc injection demonstrates stronger effects on mucosal immune response than VA supplementation.