Different cytokines are required for induction and maintenance of the Th2 type response in DBA/2 mice resistant to infection with Leishmania major

Experimental cutaneous leishmaniasis is a useful model in studying the mech anism regulating immune responses between T helper type 1 (Th1)and Th2. Mic e susceptible to Leishmania? major infection such as BALB/c (H-2(d)) are as sociated with the induction of the disease-promoting Th2 response, while th e resistant mice such as DBA/2 (H-2(d)) develop the protective Th1 response . To understand the induction mechanism of Th1 and Th2 responses, it is nec essary to establish an immunization scheme by which the induction of each T h response can be easily and experimentally controlled. Adjuvants are known to enhance the immune responses through the combined effect of several fac tors: prolonged release of antigen, migration of cells, mitogenic effect an d so forth. When the genetically resistant DBA/2 mice were immunized twice with soluble leishmanial antigen (SLA), emulsified in incomplete Freund's a djuvant (IFA) before L. major inoculation, these mice mounted a Th2 cell re sponse and suffered from progressive infection. While IL-4 and IL-lj were u pregulated early after the infection in both healer and non-healer groups o f mice, IL-5 and IL-10 were upregulated only in non-healer mice. From the s t results, IL-5 and IL-10 appear to have an important role, at least in the early phases of the infection, rather than IL-4 and IL-13 in establishing the disease-promoting Th2 response in leishmaniasis. Further, IL-9 was foun d to be expressed in both BALB/c and DBA/2 mice immunized with IFA/SLA. Thi s cytokine may support the establishment of a Th2 response in these mice. T herefore it is suggested that Th2 cytokines play different roles between pr iming and maintaining the Th2 immune response after the infection. (C) 2000 Editions scientifiques et medicales Elsevier SAS.