SEX-DETERMINED RESISTANCE AGAINST LEISHMANIA-MEXICANA IS ASSOCIATED WITH THE PREFERENTIAL INDUCTION OF A TH1-LIKE RESPONSE AND IFN-GAMMA PRODUCTION BY FEMALE BUT NOT MALE DBA 2 MICE/

Female DBA/2 mice are relatively resistant to infection with Leishmani a mexicana compared with male mice. Following subcutaneous infection w ith 5 x 10(6) L. mexicana, amastigotes lesion growth in male and femal e DBA/2 mice was measured and the developing immune responses were mon itored both in vitro and in vivo. Over the 10 week duration of the exp eriment all male DBA/2 mice developed rapidly growing non-healing lesi ons while female mice either developed no lesions whatsoever or develo ped smaller slower growing lesions than males. Both male and female mi ce produced parasite specific IgG2a during the course of the disease. However, significant titres of parasite specific IgG1 antibodies could be detected only in male mice indicating a Th2-influenced response in this sex. Furthermore, female mice, unlike male mice, developed signi ficant parasite induced cutaneous delayed-type hypersensitivity footpa d responses, indicating a Th1-influenced response in female mice. Alth ough both male and female DBA/2 mice infected with L. mexicana display ed a significant increase in the number of cells in their draining lym ph nodes at week 10 post-infection, no significant differences could b e observed in the numbers of CD4(+), CD8(+) T cells as well as B cells between male and female DBA/2 mice. However, following in vitro stimu lation, the lymph node cells from female mice displayed significantly higher antigen specific proliferative responses than the males and pro duced significant amounts of IFN-gamma which could not be detected in the equivalent culture supernatants from male mice. There were no sign ificant differences in the levels of Th2-associated cytokines IL-4 and IL-5, produced by the lymph node cells of both sexes. Treatment of fe male DBA/2 mice with IFN-gamma neutralizing antibody following L. mexi cana infection resulted in lesion growth equivalent to male mice. Conv ersely, intralesional injections of murine recombinant IFN-gamma signi ficantly inhibited lesion growth in male mice.