J. Exp. Med., Volume 188, Number 5, September 7, 1998 867-876

CD161 (NKR-P1A) Costimulation of CD1d-dependent Activation of Human T Cells Expressing Invariant V24JQ T Cell Receptor  Chains

By Mark Exley,^*§ Steven Porcelli,^§ Margo Furman,^*§ Jorge Garcia,^*§ and 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

A population of human T cells expressing an invariant V24JQ T cell antigen receptor (TCR)  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 (V24^invt 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 V24^invt T cells. However, in contrast to results in the mouse, ligation of CD161 in the absence of TCR stimulation did not result in V24^invt T cell activation, and costimulation through CD161 did not cause polarization of the cytokine secretion pattern. CD161 monoclonal antibodies specifically inhibited V24^invt 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 V24^invt T cells, which involved a granule-mediated exocytotic mechanism, was CD161-independent. In further contrast to the mouse, the signaling pathway involved in V24^invt T cell costimulation through CD161 did not appear to involve stable association with tyrosine kinase p56^Lck. These results demonstrate a role for CD161 as a novel costimulatory molecule for TCR-mediated recognition of CD1d by human V24^invt T cells.

CD1d;  CD161;  costimulation;  V24JQ;  T cells

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