Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
2.
Eur J Immunol ; 32(3): 858-67, 2002 03.
Article in English | MEDLINE | ID: mdl-11870630

ABSTRACT

In humans infected with lymphatic filariasis, microfilaraemia [the presence of microfilariae (Mf) in the blood] is generally associated with both poor antigen (Ag)-specific proliferative responses and with protection from severe disease. Clonal deletion has been suggested as one possible mechanism by which parasite-reactive lymphocytes, that may be capable of mediating resistance and/or immunopathology, are silenced in asymptomatic carriers. In this study we demonstrate that splenic lymphocytes from mice infected with microfilariae of Brugia pahangi display an Ag-specific proliferative defect. However, these cells were not completely unresponsive since they produced high levels of Ag-specific IFN-gamma. Using TdT-mediated dUTP-biotin nick end labeling for flow cytometry, CD4(+) lymphocytes from Mf-infected mice cultured with Ag showed high levels of apoptosis when compared to those from L3-infected mice which proliferated well in response to Ag. Treatment of Ag-stimulated cultures with aminoguanidine (AMG), an inhibitor of inducible nitric oxide synthase, rescued the CD4(+) T cells from apoptosis and reversed the proliferative defect. Furthermore, carboxyfluorescein diacetate succinimidyl ester labeling allowed the visualization of dividing CD4(+) T cells in cultures from Mf-infected animals only in the presence of AMG. We hypothesize that CD4(+) T cells indirectly trigger their own apoptosis by secreting significant quantities of IFN-gamma resulting in the induction of high levels of nitric oxide, and the subsequent elimination of effector T cells. Our findings are the first direct evidence that infection with Brugia Mf can selectively induce lymphocyte apoptosis, a phenomenon that could contribute to the proliferative defect and parasite persistence associated with the microfilaraemic state in the infected human.


Subject(s)
Apoptosis , Brugia pahangi/physiology , CD4-Positive T-Lymphocytes/pathology , Filariasis/immunology , Microfilariae/physiology , Aedes/parasitology , Animals , Antigens, Helminth/immunology , Brugia pahangi/growth & development , CD4-Positive T-Lymphocytes/enzymology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cells, Cultured/drug effects , Enzyme Inhibitors/pharmacology , Filariasis/pathology , Flow Cytometry , Fluoresceins/analysis , Fluorescent Dyes/analysis , Gerbillinae , Guanidines/pharmacology , Immunologic Deficiency Syndromes/etiology , Immunologic Deficiency Syndromes/parasitology , Interferon-gamma/biosynthesis , Mice , Mice, Inbred BALB C , Nitric Oxide/physiology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/physiology , Nitric Oxide Synthase Type II , Parasitemia/immunology , Parasitemia/pathology , Spleen/pathology , Succinimides/analysis , Th2 Cells/immunology , Th2 Cells/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...