Investigating the impact of helminth products on immune responsiveness using a TCR transgenic adoptive transfer system.
Helminth infections and their products have a potent immunomodulatory effect on the host immune system and can impair immune responses against unrelated Ags. In vitro studies have suggested that the immunomodulation by helminth extracts may be the result of bystander response bias toward a Th2 phenotype and/or an Ag-specific T lymphocyte proliferative hyporesponsiveness. The aim of this study was to determine the role of these potential mechanisms of immunosuppression in vivo. Therefore, using a sensitive model of CFSE-labeled OVA-specific TCR transgenic T lymphocyte adoptive transfer, we analyzed the effect of Ascaris suum body fluid (ABF) on the kinetics and amplitude of a primary OVA-specific T cell response as well as the Th1/Th2 profile of the response in wild-type and IL-4 knockout (KO) mice. We find that inhibition of delayed-type hypersensitivity by ABF was associated with a Th1/Th2 shift in wild-type animals, but not in IL-4 KO mice. The use of this model has allowed us to demonstrate that although the kinetics of the OVA-specific primary response was not affected by ABF, the expansion of the OVA-specific T lymphocytes was significantly inhibited in both wild-type and IL-4 KO mice. This inhibition was associated with a reduced proliferative capacity of these cells in vivo, distinct from anergy.
Boitelle
Agnès
A
Department of Immunology, University of Strathclyde, Glasgow, United Kingdom.
Scales
Hannah E
HE
Di Lorenzo
Caterina
C
Devaney
Eileen
E
Kennedy
Malcolm W
MW
Garside
Paul
P
Lawrence
Catherine E
CE
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D017165:Ascaris suum / Q000276:immunology*; D001826:Body Fluids / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007275:Injections, Intravenous; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000037:antagonists & inhibitors / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D010047:Ovalbumin