Mechanisms of the natural reactivity of lymphocytes from noninfected individuals to membrane-associated Leishmania infantum antigens.
Membrane-associated Leishmania Ags (MLA) or soluble Leishmania Ags were used in vitro to stimulate cord blood or PBMC from healthy donors noninfected by Leishmania parasites. MLA, but not soluble Leishmania Ags, constantly induce strong proliferation of cord blood mononuclear cells and PBMC from noninfected individuals. Responding cells are CD3+, CD4+, TCRalphabeta+, CD45RO+, and CD45RA+ and secrete IFN-gamma and IL-10, but not IL-4. MLA do not activate NK cells nor NKT cells. Membrane Ags also induce purified macrophages from noninfected individuals to secrete IL-10 and TNF-alpha, but have no effect on IL-1alpha or IL-12 secretion. The effects of MLA are proteinase K-sensitive and resistant to lipid extraction. The lymphoproliferative responses are inhibited by anti-HLA-DR Abs and require Ag processing by APCs, excluding that the biological effect of MLA could be attributed to a superantigen. Finally, TCR repertoire analysis shows that the T cell expansion induced by MLA uses TCR with various variable beta segment rearrangements and CDR3 lengths, features much more characteristic to those observed with a polyclonal activator than with a conventional Ag. These results suggest a particular mechanism developed during the host's natural response to Leishmania parasites that allows direct activation of naive CD4 lymphocytes by parasite membrane-associated Ags.
Sassi
Atfa
A
Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire, Laboratoire International Associé Bioingénierie Moléculaire, Institut Pasteur de Tunis, Tunis, Tunisia.
Larguèche-Darwaz
Beya
B
Collette
Alexis
A
Six
Adrien
A
Laouini
Dhafer
D
Cazenave
Pierre André
PA
Dellagi
Koussay
K
D000328:Adult; D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007231:Infant, Newborn; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta