T cell mechanisms in experimental autoimmune uveoretinitis: susceptibility is a function of the cytokine response profile.

This study addresses the question whether susceptibility versus resistance to experimental autoimmune uveoretinitis (EAU) is connected to a Th1-type (interferon-gamma high, interleukin-4 low), versus a Th2-type (IFN-gamma low, IL-4 high) response. Primed lymph node cells of susceptible Lewis rats produced IFN-gamma in response to antigen in culture and transferred EAU to syngeneic recipients, whereas lymph node cells of resistant F344 rats made no IFN-gamma and did not transfer disease. Reversal of the disease pattern, by treatment of F344 rats with B. pertussis toxin and immunisation of Lewis rats with antigen in incomplete Freund's adjuvant, resulted in a parallel reversal of these response patterns. Neither strain produced significant IL-4 responses. A study of the response patterns in mice confirmed that high Th1 responders were susceptible, whereas low Th1 responders and Th2 responders were resistant. We conclude that susceptibility to EAU is connected with a Th1-dominant response, but resistance can involve either a 'null', F344-like response (Th1-low/Th2-low) or a Th2-dominant response.