A non-cytosolic protein of Trypanosoma evansi induces CD45-dependent lymphocyte death.
In a recent study dealing with a mouse model of Trypanosoma evansi-associated disease, a remarkable synchrony between the parasitaemia peak and the white-blood-cell count nadir was noticed. The present study was designed to establish whether there is a direct causal link between the parasite load during its exponential phase of growth and the disappearance of peripheral blood leukocytes. In vitro experiments performed with trypanosomes and purified peripheral blood mononucleated cells revealed the existence of a lymphotoxin embedded in the T. evansi membrane: a protein sensitive to serine proteases, with a molecular mass of less than 30 kDa. Lymphocytes death induced by this protein was found to depend on the intervention of a lymphocytic protein tyrosine phosphatase. When lymphocytes were exposed to increasing quantities of a monoclonal antibody raised against the extracellular portion of CD45, a transmembrane protein tyrosine phosphatase covering over 10% of the lymphocyte surface, T. evansi membrane extracts showed a dose-dependent decrease in cytotoxicity. As the regulatory functions of CD45 concern not only the fate of lymphocytes but also the activation threshold of the TCR-dependent signal and the amplitude and nature of cytokinic effects, this demonstration of its involvement in T. evansi-dependent lymphotoxicity suggests that T. evansi might manipulate, via CD45, the host's cytokinic and adaptive responses.
Antoine-Moussiaux
Nicolas
N
Department of Pathology, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Cornet
Anne
A
Cornet
François
F
Glineur
Stéphanie
S
Dermine
Martin
M
Desmecht
Daniel
D
D000818:Animals; D002452:Cell Count; D016923:Cell Death; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism* / Q000469:parasitology; D007700:Kinetics; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009500:Neutralization Tests; D009569:Nitric Oxide / Q000378:metabolism; D018512:Parasitemia; D015800:Protozoan Proteins / Q000378:metabolism*; D013154:Spleen / Q000469:parasitology / Q000473:pathology; D013997:Time Factors; D014345:Trypanosoma / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D017493:Leukocyte Common Antigens