title: Characterization and function of the NKR-P1dim/T cell receptor-alpha beta+ subset of rat T cells.
abstract: MHC-unrestricted cytotoxicity is mediated primarily by NK cells. However, some subsets of TCR-alpha beta+ and TCR-gamma delta+ T cells also have the capacity to mediate MHC-unrestricted cytotoxicity, particularly after incubation in high concentrations of IL-2. Currently, it is not known what receptors on T cells are responsible for this activity, nor whether such receptors are the same as those on NK cells. We have recently described a type II integral membrane protein, termed NKR-P1, that is expressed at high levels on rat NK cells (NKR-P1bright). NKR-P1 contains a carbohydrate recognition domain characteristic of C-type (Ca(2+)-dependent) animal lectins and is a representative member of a distinct group of this superfamily. By a variety of criteria, NKR-P1 is linked to a signaling pathway that activates NK cell lytic function. Based on its structure and function, NKR-P1 has been implicated as a candidate molecule involved in or contributing to MHC-unrestricted cytotoxicity. We describe herein the expression of NKR-P1 at low levels on a small subset of rat T cells with an NKR-P1dim/TCR-alpha beta+ phenotype and on a small subset of cells with an NKR-P1dim/TCR-alpha beta- phenotype (presumably containing gamma delta+ T cells). Before incubation with IL-2, the NKR-P1dim subsets of cells lack MHC-unrestricted cytolytic capacity and lack the capacity for reverse antibody-dependent cellular cytotoxicity (rADCC) mediated via NKR-P1. However, culture of NKR-P1dim/TCR-alpha beta+ T cells in IL-2 led to the acquisition of both MHC-unrestricted cytotoxicity and the capacity for rADCC via NKR-P1. NK-like cytolytic function was not found among IL-2-activated NKR-P1-/TCR-alpha beta+ T cells. These data suggest that expression of functional NKR-P1 (i.e., ability to signal rADCC) correlates with and potentially contributes to MHC-unrestricted cytotoxicity.
authors.affiliation: Pittsburgh Cancer Institute, PA 15213.
authors.forename: C
authors.initials: C
authors.lastname: Brissette-Storkus
authors.forename: C L
authors.initials: CL
authors.lastname: Kaufman
authors.forename: L
authors.initials: L
authors.lastname: Pasewicz
authors.forename: H M
authors.initials: HM
authors.lastname: Worsey
authors.forename: R
authors.initials: R
authors.lastname: Lakomy
authors.forename: S T
authors.initials: ST
authors.lastname: Ildstad
authors.forename: W H
authors.initials: WH
authors.lastname: Chambers
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism*; D018956:CD5 Antigens; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000494:pharmacology; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D018956:CD5 Antigens; D007376:Interleukin-2; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic