PRESENTATION OF THE PROTECTIVE PARASITE ANTIGEN LACK BY LEISHMANIA-INFECTED MACROPHAGES

Macrophages are apparently the only cells that in vivo allow the growt h of the intracellular pathogen Leishmania. They are thus generally co nsidered as likely candidates for the presentation of parasite Ag to C D4(+) T lymphocytes known to be involved in protective and counterprot ective immune responses. In the present study, we examined whether mou se macrophages infected with Leishmania were capable of stimulating T cell hybrids and a T cell clone reacting with the previously identifie d protective Ag LACK (Leishmania homologue of receptors for Activated C Kinase), This parasite protein is expressed in both promastigote and amastigote stages of Leishmania. We found that IFN-gamma-treated macr ophages recently infected with live Leishmania promastigotes were full y competent to activate LACK-reactive T cells. However, at later times of infection, permissive macrophages infected with promastigotes were no longer able to present LACK, in spite of the presence of numerous intracellular parasites. This punctual presentation of LACK was appare ntly linked with the destruction, at least partial, of the intracellul ar parasites, In contrast, macrophages infected with live Leishmania a mastigotes were always unable to stimulate the LACK-specific T cells, Amastigote-infected macrophages could, however, reactivate the T cells if LACK-Delta 1, a recombinant form of LACK, was added as an exogenou s protein in the culture medium, Similar results were obtained with ai l combinations tested involving macrophages from various origins, diff erent activating cytokines (IFN-gamma, granulocyte-macrophage CSF, IL- 1), several Leishmania species (L. amaronensis, L. major, L. donovani) , and 15 different LACK-reactive T cell hybrids and clones. From these data, it is tempting to propose that the differentiation of promastig otes into amastigotes, which leads to a better survival of the parasit es within macrophages, also allows them to go unnoticed by the immune system.