Abstract
Purpose: :
Pertussis toxin (PTX), an exotoxin of Bordetella Pertussis, enhances development of experimental autoimmune uveitis (EAU) in a murine model. It is believed to open the blood eye barrier, which is a critical step in the development of EAU. Infiltration of immune cells across this barrier results in access to uvetogenic epitopes. PTX may also have an adjuvant-like effect on immune cells thus enhancing EAU. Accordingly we evaluated the effect of PTX on immune responses in EAU-susceptible mice.
Methods: :
B10.RIII mice were injected (s.c.) with interphotoreceptor retinoid binding protein (IRBP) and complete Freud’s adjuvant (CFA) and varying doses of PTX (i.p.). Delayed type hypersensitivity (DTH) to IRBP was quantified along with target organ damage to the retina. Splenocytes from these mice were stimulated in vitro and TNF-alpha and IFN-gamma measured in the culture supernatants.
Results: :
The DTH response to IRBP was generated by immunization with CFA and IRBP peptide in mice. Mice that were injected with PTX along with IRBP and CFA demonstrated a dose-dependant reduction of swelling 48 and 72 h after challenge with IRBP. Immunization of mice with IRBP and CFA along with an injection of PTX led to EAU as documented by histopathology of the retina. Splenocytes from these mice demonstrated enhanced TNF-alpha and IFN-gamma production as compared to the PTX-untreated mice.
Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • autoimmune disease