CD161 (NKR-P1A) Costimulation of CD1d-dependent Activation of Human T Cells Expressing Invariant Vα24JαQ T Cell Receptor α Chains (original) (raw)
Article| September 07 1998
From the *Department of Cancer Biology, Hematology/Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215; the ‡Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02215; and the §Harvard Medical School, Boston, Massachusetts 02115
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From the *Department of Cancer Biology, Hematology/Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215; the ‡Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02215; and the §Harvard Medical School, Boston, Massachusetts 02115
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From the *Department of Cancer Biology, Hematology/Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215; the ‡Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02215; and the §Harvard Medical School, Boston, Massachusetts 02115
Search for other works by this author on:
From the *Department of Cancer Biology, Hematology/Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215; the ‡Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02215; and the §Harvard Medical School, Boston, Massachusetts 02115
Search for other works by this author on:
From the *Department of Cancer Biology, Hematology/Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215; the ‡Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02215; and the §Harvard Medical School, Boston, Massachusetts 02115
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Mark Exley, Steven Porcelli, Margo Furman, Jorge Garcia, Steven Balk
From the *Department of Cancer Biology, Hematology/Oncology, Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215; the ‡Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02215; and the §Harvard Medical School, Boston, Massachusetts 02115
Address correspondence to M. Exley, Cancer Biology, Hematology/Oncology, HIM 1047, Beth Israel-Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Phone: 617-667-0982; Fax: 617-667-0610; E-mail: [email protected]
For antibody and/or cell reagents, we wish to thank Drs. A. Bendelac, J. Hansen, R. Kurrle, L. Lanier, A. Lanzavecchia, M. Lopez-Botet, D. Olive, A. Poggi, E. Reinherz, M. Robertson, and J. Ritz. We would also like to thank Drs. S.B. Wilson, S. Kent, R. Blumberg, and our colleagues in the Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, especially J. Gumperz and D.B. Moody, for unpublished results, advice, or comments on the manuscript.
Received: April 08 1998
Revision Received: June 12 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1998) 188 (5): 867–876.
A population of human T cells expressing an invariant Vα24JαQ T cell antigen receptor (TCR) α chain and high levels of CD161 (NKR-P1A) appears to play an immunoregulatory role through production of both T helper (Th) type 1 and Th2 cytokines. Unlike other CD161+ T cells, the major histocompatibility complex–like nonpolymorphic CD1d molecule is the target for the TCR expressed by these T cells (Vα24invt T cells) and by the homologous murine NK1 (NKR-P1C)+ T cell population. In this report, CD161 was shown to act as a specific costimulatory molecule for TCR-mediated proliferation and cytokine secretion by Vα24invt T cells. However, in contrast to results in the mouse, ligation of CD161 in the absence of TCR stimulation did not result in Vα24invt T cell activation, and costimulation through CD161 did not cause polarization of the cytokine secretion pattern. CD161 monoclonal antibodies specifically inhibited Vα24invt T cell proliferation and cytokine secretion in response to CD1d+ target cells, demonstrating a physiological accessory molecule function for CD161. However, CD1d-restricted target cell lysis by activated Vα24invt T cells, which involved a granule-mediated exocytotic mechanism, was CD161-independent. In further contrast to the mouse, the signaling pathway involved in Vα24invt T cell costimulation through CD161 did not appear to involve stable association with tyrosine kinase p56Lck. These results demonstrate a role for CD161 as a novel costimulatory molecule for TCR-mediated recognition of CD1d by human Vα24invt T cells.
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