T-cell responses to immunodominant LACK antigen do not play a critical role in determining susceptibility of BALB/c mice to Leishmania mexicana

Although BALB/c mice develop lesions when infected with Leishmania mexicana , the mechanisms which are responsible for susceptibility to this parasite have not been elucilaated. In contrast, susceptibility of BALB/c mice to Le ishmania major has been shown to depend on the early production of interleu kin-4 (IL-4) by T cells which react to the parasitic LACK antigen. Here, we demonstrate that the lesions induced by L. mexicana are delayed compared t o those induced by L. major but rapidly develop at later time points. Inter estingly, while LACK-tolerant BALB/c-derived IE-LACK transgenic mice were r esistant to L. major, they were susceptible to L. mexicana and developed le sions similar to those observed in wild-type BALB/c mice. The latter result was observed despite the fact that (i) LACK was expressed by L mexicana, ( ii) splenocytes from BALB/c mice were able to stimulate LACK-specific T-cel l hybridoma cells when incubated with live L. mexicana promastigotes, and ( iii) LACK-specific T cells contributed to IL-4 production in L. mexicana-in fected BALB/c mice. Thus, in contrast to what was observed for L. major-inf ected mice, LACK-specific T cells do not play a critical role in determinin g susceptibility to L. mexicana. Although BALB/c mice :are susceptible to b oth L. major and L. mexicana, the mechanisms which are responsible for susc eptibility to these parasites are likely to be different.