The protective Th1 response in mice is induced in the T-cell zone only three weeks after infection with Leishmania major and not during early T-cell activation.

The protozoan parasite Leishmania spp. causes clinical pictures ranging in severity from spontaneously healing skin ulcers to systemic disease. The immune response associated with healing involves the differentiation of IFNγ-producing Th1 cells, whereas the non-healing phenotype is associated with IL4-producing Th2 cells. The widespread assumption has been that the T-cell differentiation that leads to a healing or non-healing phenotype is established at the time of T-cell activation early after infection. By selectively analyzing the expression of cytokine genes in the T-cell zones of lymph nodes of resistant (Th1) C57BL/6 mice and susceptible (Th2) BALB/c mice during an infection with Leishmania major in vivo, we show that the early T-cell response does not differ between C57BL/6 mice and BALB/c mice. Instead, Th1/Th2 polarization appears suddenly 3 weeks after infection. At the same time point, the number of parasites increases in lymph nodes of both mouse strains, but about 100-fold more in susceptible BALB/c mice. We conclude that the protective Th1 response in C57BL/6 mice is facilitated by the capacity of their innate effector cells to keep parasite numbers at low levels.