INTERFERON-GAMMA AND INTERLEUKIN-4 IN HUMAN LEISHMANIA-DONOVANI INFECTIONS

Clinical and immunological similarities between Leishmania donavani in fections in humans and L. major infections in mice suggest that some o f the pathophysiological mechanisms are the same in the two conditions . Both infections can result either in a fatal systemic disease or in a self-limiting infection with few and mild symptoms. In the murine mo del the outcome of the infection is critically related to the cytokine s produced by T lymphocytes activated by leishmanial antigens. Activat ion of the IFN-gamma producing Th1 subset of CD4 positive T cells resu lts in cure and survival, whereas activation of the IL-4 secreting Th2 subset results in a progressive disease with fatal outcome. A similar Th1/Th2 dichotomy in the cytokine response to L. donovani may exist i n humans, and may have influence on the outcome of infection. In murin e leishmaniasis the levels of IL-4 and IFN-gamma at the time of infect ion can direct the T cell response into Th1 or Th2 type. If similar me chanisms operate in humans, the outcome of L. donovani infections may depend on the local cytokine environment in which early activation of Leishmania specific T cells takes place. Cytokines secreted by cross-r eactive memory T cells, activated by antigens from the invading micro- organism, may contribute to determine this environment.