Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ.
We previously reported that Trypanosoma cruzi, the agent of Chagas disease, induces in congenitally infected fetuses a strong, adult-like parasite-specific CD8(+) T cell response producing IFN-γ (Hermann et al. in Blood 100:2153-2158, 2002). This suggests that the parasite is able to overcome the immaturity of neonatal antigen presenting cells, an issue which has not been previously addressed. We therefore investigated in vitro the ability of T. cruzi to activate cord blood DCs and compared its effect to that on adult cells. We show that T. cruzi induces phenotypic maturation of cord blood CD11c(+) myeloid DCs (mDCs), by enhancing surface expression of CD40, CD80, and CD83, and that parasite-specific IgG purified from cord blood of neonates born to T. cruzi-infected mothers amplify such expression. CD83, considered as the best marker of mature DCs, reaches higher level on cord blood than on adult mDCs. Allo-stimulation experiments showed that T. cruzi-activated cord blood mononuclear cells enriched in DCs (eDCs) stimulate proliferation of cord blood and adult CD3(+) T cells to a similar extent. Of note, T. cruzi-activated eDCs from cord blood trigger more potent proliferation of CD8(+) than CD8(-) (mainly CD4(+)) adult T cells, a feature not observed with adult eDCs. T cell proliferation is associated with IFN-γ release and down-regulation of IL-13 production. These data show that T. cruzi potently activates human cord blood mDCs and endows eDCs to trigger CD8(+) T cell proliferation and favor type 1 immune response. Interestingly, maternal antibodies can strengthen the development of mature DCs that might contribute to overcome the immunological immaturity associated with early life.
Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles (U.L.B.), 808 Route de Lennik, CP 616, 1070, Brussels, Belgium.
Patricia
P
Rodriguez
Yves
Y
Carlier
Carine
C
Truyens
D000328:Adult; D000913:Antibodies, Protozoan / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism*; D018793:Interleukin-13 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D014349:Trypanosoma cruzi / Q000276:immunology*; D000097802:CD83 Antigen
D000913:Antibodies, Protozoan; D015703:Antigens, CD; D018122:B7-1 Antigen; D019013:CD40 Antigens; D007136:Immunoglobulins; D007371:Interferon-gamma; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen