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Trichuris muris: CD4+ T cell-mediated protection in reconstituted SCID mice

  • C. J. BETTS (a1) (a2), M. L. deSCHOOLMEESTER (a1) and K. J. ELSE (a1)

Abstract

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 × 106 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-β7, anti-MAdCAM-1 and anti-αE), 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.

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Corresponding author

Corresponding author: Tel: +0161 275 5235. Fax: +0161 275 5640. E-mail: Kathryn.J.Else@man.ac.uk

Keywords

Trichuris muris: CD4+ T cell-mediated protection in reconstituted SCID mice

  • C. J. BETTS (a1) (a2), M. L. deSCHOOLMEESTER (a1) and K. J. ELSE (a1)

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