title: Proline-rich tyrosine kinase-2 is critical for CD8 T-cell short-lived effector fate.
abstract: T-cell interactions with antigen-presenting cells are important for CD8 T-cell effector or memory fate determination. The integrin leukocyte function-associated antigen-1 (LFA-1) mediates T-cell adhesion but the contribution of LFA-1-induced signaling pathways to T-cell responses is poorly understood. Here we demonstrate that proline-rich tyrosine kinase-2 (PYK2) deficiency impairs CD8 T-cell activation by synergistic LFA-1 and T-cell receptor stimulation. Furthermore, PYK2 is essential for LFA-1-mediated CD8 T-cell adhesion and LFA-1 costimulation of CD8 T-cell migration. During lymphocytic choriomeningitis virus infection in vivo, PYK2 deficiency results in a specific loss of short-lived effector CD8 T cells but does not affect memory-precursor CD8 T-cell development. Similarly, lack of LFA-1 primarily impairs the generation of short-lived effector cells. Thus, PYK2 facilitates LFA-1-dependent CD8 T-cell responses and promotes CD8 T-cell short-lived effector fate, suggesting that PYK2 may be an interesting therapeutic target to suppress exacerbated CD8 T-cell responses.
authors.affiliation: Department of Medicine, Division of Rheumatology, The Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, and Graduate Program in Biomedical Sciences, University of California, San Francisco, CA 94143-0795, USA.
authors.forename: Sören
authors.initials: S
authors.lastname: Beinke
authors.forename: Hyewon
authors.initials: H
authors.lastname: Phee
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Clingan
authors.forename: Joseph
authors.initials: J
authors.lastname: Schlessinger
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Matloubian
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured; D051418:Focal Adhesion Kinase 2 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D007156:Immunologic Memory; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse
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