T-CELL MECHANISMS IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS - SUSCEPTIBILITY IS A FUNCTION OF THE CYTOKINE RESPONSE PROFILE

This study addresses the question whether susceptibility versus resist ance 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 susce ptible 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,vith B. p ertussis toxin and immunisation of Lewis rats with antigen in incomple te Freund's adjuvant, resulted in a parallel reversal of these respons e patterns. Neither strain produced significant IL-4 responses. A stud y of the response patterns in mice confirmed that high Th1 responders were susceptible, whereas low Th1 responders and Th2 responders were r esistant. We conclude that susceptibility to EAU is connected with a T h1-dominant response, but resistance can involve either a 'null', F344 -like response (Th1-low/Th2-low) or a Th2-dominant response.