Trichuris muris: CD4+ T cell-mediated protection in reconstituted SCID mice.
Resistance to the murine intestinal nematode Trichuris muris requires the development of a strong Th2 response. In a reconstituted SCID mouse model, CD4+ Th2 cells can mediate resistance to infection in the absence of antibody (Else & Grencis, 1996). The data presented here address the issue of how CD4+ T cells mediate this protective immunity within the SCID host. These studies demonstrate that timing and cell dose are critical if transfer is to result in resistance, with a minimum of 5 x 10(6) immune donor cells required to confer immunity. Furthermore, this CD4-mediated protective immunity only operates against the larval stages of the parasite. When the molecules necessary for activated CD4+ T cell migration to the GALT are inhibited with a cocktail of anti-integrin/addressin antibodies (anti-beta7, anti-MAdCAM-1 and anti-alphaE), the resistance conferred by immune donor cells is completely abrogated. This implies that the effector mechanism acts locally at the level of the gut. CD4+ mediated cytotoxicity, directed against the epithelial cells inhabited by the parasite, could represent a novel, locally acting effector mechanism. However, Fas and Fas ligand-deficient mice, which are unable to mount CD4-mediated cytotoxic responses, readily expel T. muris indicating that the mechanism by which CD4-T cells mediate protective immunity is unlikely to involve killing of infected gut epithelial cells.
Betts
J
J
School of Biological Sciences, University of Manchester, UK. Catherine.Betts@ctl.astrazeneca.com
deSchoolmeester
M L
ML
Else
K J
KJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000032:analysis; D007413:Intestinal Mucosa / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology*
D007074:Immunoglobulin G