Resistance to Leishmania major in Mice.

to Leishmania major in mice is a topic of interest to many imMLunologists attempting to link the immunological mechanism with the responsible genes. In this respect, this experimental system is one of the paradigms for genetics of disease susceptibility. Mehmet L. Giuler et al. (1) question the hypothesis that production of in-terleUkin-4 (IL-4) with subsequent generation of a T helper cell type 2 (TH2) response is the cause of susceptibility of BALB/c mice to L. major infection. Their data show that the susceptible BALB/c mice, but not the resistant B1O.D2 mice, exhibit a diminished induction of interfer-on y (IFN-y) by IL-12 treatment, indicating a deficient TH1 response, whereas the IL-4 response is the same in both strains. This deficit in the THI response in BALB/c mice is linked to a region of chromosome 11 comprising IL-4, IRF-1, and several other immunologically relevant loci. Gtiler et al. propose that their findings are relevant for the host response to L. major infection because of the linkage between this chromosomal region and susceptibility to L. major suggested by Roberts et al. (2). They propose, therefore, that the resistance to L. major is based on maintenance of the IL-12 pathway and not on differential regulation of IL-4 production. The genetic data argue against this simple model. We analyzed the genetic differences in T cell activation and resistance to L. major between the susceptible strain BALB/ cHeA and the resistant strain STS/A using the series of 20 homozygous CcS/Dem re-combinant congenic (RC) strains. Each of the CcS/Dem strains carries a different random set of approximately 12.5% of the genes of the STS/A strain on the genetic background of the BALB/cHeA strain. Consequently, the individual loci involved in control of a multigenic trait were separated into different CcS/Dem strains, where they could be studied one by one (3). Our testing of susceptibility to L. major in the 20 CcS/Dem strains indicates that it is multi-genically controlled (4). Moreover, the most resistant RC strain, CcS-5, received the whole central and telomeric part of chromosome 11 (including the IL-4 locus and the other linked immunologically relevant loci) from the susceptible parent BALB/c (5), indicating that this region cannot be the major factor determining susceptibility of BALB/c mice. Even in the case that this region of chromosome 11 has some effect on L. major susceptibility, it has by no means been proven that this effect is based on the …