Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. II. Analysis on susceptibility to EAO induction using F1 hybrid mice and adoptive transfer system.

In our novel murine model of experimental autoimmune orchitis (EAO) induced by two or three injections of viable syngeneic testicular germ cells (TC) alone, significant differences in susceptibility to the induction of EAO were found, and the disease susceptibility did not seem to be associated with a particular H-2 haplotype. The H-2 identical background disparate (highly susceptible x low susceptible)F1 hybrids, (C3H/He x C3H/HeJ)F1 and (C3H/HeJ x C3H/He)F1 mice, were highly susceptible to the induction of EAO. The H-2 identical background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x C3H/BiKi)F1 and (C3H/BiKi x C3H/He)F1 mice, were low susceptible to the induction of EAO. Both the H-2 and background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x DBA/2N)F1 and (DBA/2N x C3H/He)F1 mice, were equally resistant to EAO induction. In the susceptible hybrids, both delayed footpad reaction (DFR) and antibody responses to TC increased. On the other hand, in the resistant hybrids, the levels of anti-TC antibodies were elevated but the DFR to TC remains depressed. This suggests that the antibody production and induction of DFR may be under different genetic controls and that cellular immunity plays an important role in this EAO induction. In order to search for the mechanistic basis for low susceptible C3H/HeJ and resistant C3H/BiKi mice, these mice received orchitis-inducible spleen cells (SPCs) from C3H/He mice. C3H/HeJ mice were highly susceptible to passive EAO. In contrast, disease-resistant C3H/BiKi mice failed to develop passive EAO. In addition, we examined whether or not regulatory cells capable of preventing the disease induction were generated in low susceptible C3H/HeJ and resistant C3H/BiKi mice immunized with TC. Transfer of SPCs from TC-immunized C3H/HeJ and C3H/BiKi mice into C3H/He mice before the EAO challenge had no suppressive effect on subsequent disease induction.