Susceptibility to Mycobacterium leprae of ALY (Alymphoplasia) mice and IFN-gamma induction in the culture supernatant of spleen cells

The alylaly (alymphoplasia) mice from a mutation of a colony of the C57BL/6 J mouse strain, which has a systemic absence of lymph nodes and Peyer's pat ches, are deficient in both T- and B-cell-mediated immune functions. We hav e undertaken a comparison of susceptibility to Mycobacterium leprae of ALY (alylaly; aly/+) mice with C57BL/6J mice. The alylaly mouse was found to ha ve an excellent high susceptibility to M. leprae with no distinction betwee n female and male. The aly/+ mouse also was more susceptible to M. leprae a t an earlier stage than the C57BL/6J mouse. Therefore, we examined and comp ared the cytokine gene expression and gamma interferon (IFN-gamma) inductio n in the splenocytes of ALY mice. The expression of interleukin 4 (IL-4), I L-10 and IL-12 mRNA was weakly stimulated with ML-lysate in inoculated alyl aly mice but IL-2, IL-6, IGIF/IL-18 and IFN-gamma mRNA were not observed. N one of the cytokine genes used appeared, except the mRNA for IL-I-a, when u ninfected cultured spleen cells were stimulated with hll-lysate. Also, IFN- gamma production was not induced. However, the appearance of these cytokine genes was observed when stimulated with concanavalin A (ConA), and IFN-gam ma production was also induced in the culture supernatant by aly/+ and even alylaly mice stimulated with ConA. To er;amine the reason why IFN-gamma ca nnot be produced by splenocytes of ALY mice inoculated with M. leprae, we d etected cytokine gene expression and IFN-gamma induction in the presence of recombinant murine IL-12 or IGIF/IL-18. IL-2 mRNA expression was detected in all of the mice tested in the presence of IL-12 but not in alylaly mice under IGIF/IL-18, and NOS mRNA expression was not observed in alylaly mice under IL-12 or IGIF/IL-18. IL-4 and IL-10 mRNA were detected by alylaly mic e only by exposure to IGIF/IL-18. III culture. the supernatant with ML anti gene of the alylaly mice did not produce IFN-gamma in spite of the presence of IL-12 and IGIF/IL-18, while IFN-gamma was weakly induced in aly/+ mice stimulated with ML-lysate and in the presence of IGIF/IL-18. Nevertheless, IFN-gamma production was observed in splenocytes of the nh alylaly mice sti mulated with ConA and also with IGIF/IL-18 plus anti-CD3 antibody. Our resu lts suggest that ALY mice might be showing a high susceptibility to M. lepr ae because of deficient priming for activation of T cells with the leprosy bacilli infection. Moreover. it is possible that the phagocytic activities of the macrophages of ALY mice are also impaired.