Showing papers by "Toshiaki Ohteki published in 1997"

Role for IL-15/IL-15 receptor beta-chain in natural killer 1.1+ T cell receptor-alpha beta+ cell development.

Abstract: Mouse TCR alphabeta+ cells expressing NKR-P1 (NK1+ T cells in the C57BL/6 strain) are classified as a unique subset that require beta2m-associated, MHC class I-like molecules for development and preferentially express particular V beta and V alphaJ domains of the TCR. We show here that NK1+ T cells express the IL-2R beta/IL-15R beta that is normally present on conventional NK cells, but not T cells. In mice lacking IL-2R beta/IL-15R beta chain, the number of NK1+ T cells is dramatically reduced. However, in IL-2-deficient mice, NK1+ T cells develop normally. Moreover, NK1+ T cells proliferate upon stimulation by IL-15, and the proliferation is blocked by the addition of anti-IL-2R beta/IL-15R beta Abs. Collectively, our data indicate that NK1+ T cells require IL-2R beta/IL-15R beta chain in an IL-2-independent manner and demonstrate that IL-15 plays a crucial role during development.

Lack of directed V alpha 14-J alpha 281 rearrangements in NK1+ T cells.

Abstract: NK1.1+ T cells are an unusual subset of TCR alpha beta cells distinguished by their highly restricted V beta repertoire and predominant usage of an invariant V alpha 14-J alpha 281 chain. To assess whether a directed rearrangement mechanism could be responsible for this invariant alpha chain, we have analyzed V alpha 14 rearrangements by polymerase chain reaction and Southern blot in a panel of cloned T-T hybrids derived from thymic NK1.1+ T cells. As expected a high proportion (17/20) of the hybrids had rearranged V alpha 14 to J alpha 281. However, V alpha 14-J alpha 281 rearrangements always occurred on only one chromosome and were accompanied by other V alpha-J alpha rearrangements (not involving V alpha 14) on the homologous chromosome. These data argue that rigorous ligand selection rather than directed rearrangement is responsible for the high frequency of V alpha 14-J alpha 281 rearrangements in NK1.1+ T cells.

Thymus-independent generation of NK1+ T cells in vitro from fetal liver precursors.

Abstract: NK1.1+TCR alpha beta+ (NK1+) T cells are an unusual subset of mouse TCR alpha beta+ cells found primarily in adult thymus and liver. In contrast to conventional TCR alpha beta+ cells, NK1+ T cells have a TCR repertoire that is highly skewed to V alpha14 and to Vbeta8, -7, and -2. The developmental origin and ligand specificity of NK1+ T cells are controversial. We show here that NK1+ T cells with a typically biased V alpha and V beta repertoire develop in cytokine-supplemented suspension cultures of fetal liver established from either normal or athymic mice. Furthermore, NK1+ T cell development in fetal liver cultures is abrogated in beta2m-deficient mice (which lack MHC class I and other related molecules) and can be partially inhibited by the presence of anti-CD1 mAbs. Moreover, mixing experiments indicate that recombination-deficient SCID fetal liver cells can reconstitute NK1+ T cell development in beta2m-deficient fetal liver cultures. Collectively, our data demonstrate that NK1+ T cells can develop extrathymically from fetal liver precursors and that a beta2m-associated ligand (putatively CD1) present on nonlymphoid cells is essential for their positive selection and/or expansion.

Natural killer-like T cells develop in SJL mice despite genetically distinct defects in NK1.1 expression and in inducible interleukin-4 production.

Abstract: An unusual subset of mature T cells expresses natural killer (NK) cell-related surface markers such as interleukin-2 receptor beta (IL-2R beta; CD122) and the polymorphic antigen NK1.1. These "NK-like" T cells are distinguished by their highly skewed V alpha and V beta repertoire and by their ability to rapidly produce large amounts of IL-4 upon T cell receptor (TCR) engagement. The inbred mouse strain SJL (which expresses NK1.1 on its NK cells) has recently been reported to lack NK1.1+ T cells and consequently to be deficient in IL-4 production upon TCR stimulation. We show here, however, that SJL mice have normal numbers of IL-2R beta+ T cells with a skewed V beta repertoire characteristic of "NK-like" T cells. Furthermore lack of NK1.1 expression on IL-2R beta+ T cells in SJL mice was found by backcross analysis to be controlled by a single recessive gene closely linked to the NKR-P1 complex on chromosome 6 (which encodes the NK1.1 antigen). Analysis of a panel of inbred mouse strains further demonstrated that lack of NK1.1 expression on IL-2R beta+ T cells segregated with NKR-P1 genotype (as assessed by restriction fragment length polymorphism) and thus was not restricted to the SJL strain. In contrast, defective TCR induced IL-4 production (which appeared to be a unique property of SJL mice) seems to be controlled by two recessive genes unlinked to NKR-P1. Collectively, our data indicate that "NK-like" T cells develop normally in SJL mice despite genetically distinct defects in NK1.1 expression and inducible IL-4 production.

Altered peptide ligands trigger perforin- rather than Fas-dependent cell lysis.

Abstract: CTLs lyse Fas-expressing target cells by the concomitant action of a perforin- and a Fas-dependent mechanism. This study analyzed whether target cells pulsed with T cell antagonists and other altered peptide ligands (APLs) were susceptible selectively to only one of these two mechanisms. In vivo and in vitro activated T cells from transgenic mice expressing a TCR specific for lymphocytic choriomeningitis virus were used as effector cells. To distinguish between perforin- and Fas-dependent cytotoxicity, T cells from normal or perforin-deficient mice were used to lyse peptide-pulsed Fas-positive or Fas-negative target cells. In contrast to previous reports that have shown that APLs selectively induce the Fas-dependent pathway of cytotoxicity, our results demonstrate that target cells pulsed with T cell antagonists and other APLs are lysed predominantly by the perforin-dependent pathway. The contribution of Fas-mediated cytotoxicity was similar for the full agonist and the APLs. Thus, full agonists, partial agonists, and antagonists trigger similar and not distinct pathways of cytotoxicity.