title: Specificity for the tumor-associated self-antigen WT1 drives the development of fully functional memory T cells in the absence of vaccination.
abstract: Recently, vaccines against the Wilms Tumor antigen 1 (WT1) have been tested in cancer patients. However, it is currently not known whether physiologic levels of WT1 expression in stem and progenitor cells of normal tissue result in the deletion or tolerance induction of WT1-specific T cells. Here, we used an human leukocyte antigen-transgenic murine model to study the fate of human leukocyte antigen class-I restricted, WT1-specific T cells in the thymus and in the periphery. Thymocytes expressing a WT1-specific T-cell receptor derived from high avidity human CD8 T cells were positively selected into the single-positive CD8 population. In the periphery, T cells specific for the WT1 antigen differentiated into CD44-high memory phenotype cells, whereas T cells specific for a non-self-viral antigen retained a CD44(low) naive phenotype. Only the WT1-specific T cells, but not the virus-specific T cells, displayed rapid antigen-specific effector function without prior vaccination. Despite long-term persistence of WT1-specific memory T cells, the animals did not develop autoimmunity, and the function of hematopoietic stem and progenitor cells was unimpaired. This is the first demonstration that specificity for a tumor-associated self-antigen may drive differentiation of functionally competent memory T cells.
authors: Department of Immunology, University College London, Royal Free Hospital, London, UK.
authors: Constandina
authors: C
authors: Pospori
authors: Shao-An
authors: SA
authors: Xue
authors: Angelika
authors: A
authors: Holler
authors: Cecile
authors: C
authors: Voisine
authors: Mario
authors: M
authors: Perro
authors: Judith
authors: J
authors: King
authors: Farnaz
authors: F
authors: Fallah-Arani
authors: Barry
authors: B
authors: Flutter
authors: Ronjon
authors: R
authors: Chakraverty
authors: Hans J
authors: HJ
authors: Stauss
authors: Emma C
authors: EC
authors: Morris
mesh_terms: D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D014611:Vaccination; D025721:WT1 Proteins / Q000235:genetics / Q000276:immunology*; D009396:Wilms Tumor / Q000276:immunology
chemical_list: D025721:WT1 Proteins