Presentation of the protective parasite antigen LACK by Leishmania-infected macrophages.
Macrophages are apparently the only cells that in vivo allow the growth of the intracellular pathogen Leishmania. They are thus generally considered as likely candidates for the presentation of parasite Ag to CD4+ T lymphocytes known to be involved in protective and counterprotective immune responses. In the present study, we examined whether mouse macrophages infected with Leishmania were capable of stimulating T cell hybrids and a T cell clone reacting with the previously identified 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 macrophages recently infected with live Leishmania promastigotes were fully 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 apparently linked with the destruction, at least partial, of the intracellular parasites. In contrast, macrophages infected with live Leishmania amastigotes 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 exogenous protein in the culture medium. Similar results were obtained with all combinations tested involving macrophages from various origins, different activating cytokines (IFN-gamma, granulocyte-macrophage CSF, IL-4), several Leishmania species (L. amazonensis, 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 promastigotes into amastigotes, which leads to a better survival of the parasites within macrophages, also allows them to go unnoticed by the immune system.
Prina
E
E
Unit of Cellular Immunophysiology, Pasteur Institute, Paris, France.
Lang
T
T
Glaichenhaus
N
N
Antoine
J C
JC
D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000378:metabolism*; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006822:Hybrid Cells; D066298:In Vitro Techniques; D007891:Leishmania / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D007896:Leishmaniasis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania