Genetic Susceptibility to the Induction of Murine Experimental Autoimmune Orchitis (EAO) without Adjuvant. I. Comparison of Pathology, Delayed Type Hypersensitivity, and Antibody

Abstract

In the present study, it was demonstrated that there were marked strain differences in susceptibility to the induction of our new murine model of experimental autoimmune orchitis (EAO; definite orchitis with hypospermatogenesis) induced by two or three sc injections with viable syngeneic testicular germ cells (TC) without any adjuvants. Among 12 inbred strains of mice examined, the A/J (H-2 a), C3H/He (H-2 k), and C3H/HeN (H-2 k) strains were highly susceptible, whereas the C57BL/6N (H-2 b), C57BL/10Sn (H-2 b), BALB/cAnN (H-2 d), AKR/N (H-2 k), CBA/JN (H-2 k), C3H/HeJ (H2 k), and MRL/ lpr (H-2 k) strains were low susceptible, and the DBA/2N (H-2 d) as well as C3H/BiKi (H-2 k) strains were resistant. In particular, mice of the H-2 k haplotype demonstrated varying degrees of susceptibility, from highly to totally resistant, to the induction of EAO. Disease susceptibility to this type of EAO does not seem to be associated with a particular H-2 haplotype. All mice of the highly susceptible strains that received two injections of TC (TC×2) developed a significant increase in both levels of delayed footpad reaction (DFR) to TC and anti-TC antibodies measured by ELISA. In the low susceptible and the resistant strains receiving TC×2 or TC×3, there was no correlation between the immune responses and the susceptibility to disease in these strains, with the exception of the BALB/cAnN mice receiving TC×3. The low susceptible and the resistant mice that received TC×2 were classified into four groups based on the DFR and antibody response: the C57BL/6N, BALB/cAnN, CBA/JN, and C3H/HeJ strains were both positive, and the C57BL/10Sn and AKR/N strains were both negative or very low; the DBA/2N and MRL/ lpr strains showed negative DFR and positive antibody response, and the C3H/BiKi strain showed quite the opposite. Almost all mice of the 12 inbred strains that received TC×3 showed positive antibody response, although its level varied. There seems to be no linkage between the cell-mediated and humoral immune responses and the H-2 locus in our new EAO model.