title: CD1d expression on chronic lymphocytic leukemia B cells affects disease progression and induces T cell skewing in CD8 positive and CD4CD8 double negative T cells.
abstract: Chronic lymphocytic leukemia develops within a complex network driven by genetic mutations and microenvironmental interactions. Among the latter a complex interplay with the immune system is established by the clone. Next to a proposed recruitment of support from T and myeloid cells, potential anti-CLL immune reactions need to be subverted. By using TCL1 mice as a CLL model, we show that TCR-Vβ7+ NK1.1+ T cells are overrepresented in this disease model and constitute a main subset of peripheral CD3+ cells with biased TCR usage, showing that these cells account for a major part for T cell skewing in TCL1 mice. Moreover, we show that overrepresentation is dependent on CD1d expression in TCL1 mice, implicating that these cells belong to a NKT-like cell fraction which are restricted to antigen presented by the MHC-like surface marker CD1d. Accordingly, we observed a high fraction of CD161+ cells within overrepresented T cells in CLL patients and we found downregulation of CD1d on the surface of CLL cells, both in TCL1 mice and patients. Finally, we show that in TCL1 mice, CD1d deficiency resulted in shortened overall survival. Our results point to an interaction between CLL and CD161+ T cells that may represent a novel therapeutic target for immune modulation.
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Nadja
authors.initials: N
authors.lastname: Zaborsky
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Franz Josef
authors.initials: FJ
authors.lastname: Gassner
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Asslaber
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Reinthaler
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Denk
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Flenady
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Josefina Piñón
authors.initials: JP
authors.lastname: Hofbauer
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Danner
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rebhandl
authors.affiliation: Department of Neurology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Harrer
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Geisberger
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.|Salzburg Cancer Research Institute, Salzburg, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Egle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009154:Mutation; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000166:cytology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D017252:CD3 Complex; C526879:Cd1d1 protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell
keywords: CD161; CD1d; CLL; T cell skewing; T cells