Extrathymic development of V alpha 14-positive T cells.

Makino, Yuko; Yamagata, N.; Sasho, Takahisa; Adachi, Yoshihiro; Kanno, Rieko; Koseki, Haruhiko; Kanno, Morio; Taniguchi, Masaru

doi:10.1084/jem.177.5.1399

Cited by 130 publications

(84 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phenotypically, they are different from thymic NKT cells (36), and they may be extrathymically derived (37). Although almost 30% of BM NKT cells have been shown to bind CD1d tetramers (35), they are not stimulated with ␣-GalCer at all in this study.…”

Section: Discussionmentioning

confidence: 56%

Regulation of NKT Cells by Ly49: Analysis of Primary NKT Cells and Generation of NKT Cell Line

Maeda

Lohwasser

Yamamura

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

TCRαβ+NK1.1+ (NKT) cells are known to express various NK cell-associated molecules including the Ly49 family of receptors for MHC class I, but its functional significance has been unclear. Here, we examined the expression of Ly49A, C/I and G2 on various NKT cell populations from normal and MHC class I-deficient C57BL/6 mice as well as their responsiveness to α-galactosylceramide (α-GalCer), a potent stimulator of CD1d-restricted NKT cells. The frequency and the level of Ly49 expression varied among NKT cells from different tissues, and were regulated by the expression of MHC class I and CD1d in the host. Stimulation of various NKT cells with α-GalCer suggested that Ly49 expression inversely correlates with the responsiveness of NKT cells to α-GalCer. Moreover, α-GalCer presented by normal dendritic cells stimulated purified Ly49−, but not Ly49+, splenic NKT cells, whereas MHC class I-deficient dendritic cells presented α-GalCer to both Ly49+ and Ly49− NKT cells equally well. Therefore, MHC class I on APCs seems to inhibit activation of NKT cells expressing Ly49. To further characterize CD1d-restricted NKT cells, we generated an α-GalCer-responsive NKT cell line from thymocytes. The line could only be generated from Ly49−NK1.1+CD4+ thymocytes but not from other NKT cell subsets, and it lost expression of NK1.1 and CD4 during culture. Together, these results indicate the functional significance of Ly49 expression on NKT cells.

show abstract

Section: Discussionmentioning

confidence: 56%

Regulation of NKT Cells by Ly49: Analysis of Primary NKT Cells and Generation of NKT Cell Line

Maeda

Lohwasser

Yamamura

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…It was notable that NKT cells did not express CD27, which has been implicated in activation of T cells and NK cells (38,39) and T cell differentiation (40). This may be due to the unique ontogeny of NKT cells, which is distinct from conventional T cells (1,2,41).…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of Th1 and Th2 Functions of NKT Cells by CD28 and CD40 Costimulatory Pathways

Hayakawa

Takeda

Yagita

et al. 2001

The Journal of Immunology

182

179

View full text Add to dashboard Cite

Vα14 NKT cells produce large amounts of IFN-γ and IL-4 upon recognition of their specific ligand α-galactosylceramide (α-GalCer) by their invariant TCR. We show here that NKT cells constitutively express CD28, and that blockade of CD28-CD80/CD86 interactions by anti-CD80 and anti-CD86 mAbs inhibits the α-GalCer-induced IFN-γ and IL-4 production by splenic Vα14 NKT cells. On the other, the blockade of CD40-CD154 interactions by anti-CD154 mAb inhibited α-GalCer-induced IFN-γ production, but not IL-4 production. Consistent with these findings, CD28-deficient mice showed impaired IFN-γ and IL-4 production in response to α-GalCer stimulation in vitro and in vivo, whereas production of IFN-γ but not IL-4 was impaired in CD40-deficient mice. Moreover, α-GalCer-induced Th1-type responses, represented by enhanced cytotoxic activity of splenic or hepatic mononuclear cells and antimetastatic effect, were impaired in both CD28-deficient mice and CD40-deficient mice. In contrast, α-GalCer-induced Th2-type responses, represented by serum IgE and IgG1 elevation, were impaired in the absence of the CD28 costimulatory pathway but not in the absence of the CD40 costimulatory pathway. These results indicate that CD28-CD80/CD86 and CD40-CD154 costimulatory pathways differentially contribute to the regulation of Th1 and Th2 functions of Vα14 NKT cells in vivo.

show abstract

“…Tumor specimens were also obtained from cancer tissue of the removed lung. Genomic DNA was prepared as described 24 and used for PCR with primers for V␣24 and J␣Q. To obtain a standard curve, 2.7 ϫ 10 3 copy numbers of PCR products amplified with V␣24 J␣Q primer pairs were serially diluted and subjected to PCR with a V␣24 (5Ј-TGGGAGAGGTCCTGTTTCCCTGAC) and J␣Q (3Ј-AGGCCA-GACAGTCAACTGAG) primer pair.…”

Section: Quantification Of V␣24 Nkt Cells In Human Lung Tissue and Tumormentioning

confidence: 99%

Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients

Motohashi

Kobayashi

Ito

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

Human V␣24 NKT cells bearing an invariant V␣24J␣Q antigen receptor, the counterpart of murine V␣14 NKT cells, are activated by a specific ligand, ␣-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating V␣24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, V␣24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of V␣24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of V␣14 NKT cells in the mouse lung. Levels of V␣24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of ␣-GalCer-pulsed DCs expanded V␣14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that ␣-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of ␣-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous V␣24 NKT cells in the lung of cancer patients is discussed. © 2002 Wiley-Liss, Inc. Key words: V␣24 NKT cell; IFN-␥ primary lung cancer; ␣-galactosylceramide; single-cell sorting RT-PCRMurine V␣14 NKT cells are characterized by coexpression of NK1.1, an NK cell marker, and an invariant antigen receptor encoded by V␣14 and J␣281 gene segments. 1-3 V␣14 NKT cells recognize a glycolipid, ␣-GalCer, in a CD1d-depenent fashion. 4 The CD1d molecule has been well conserved throughout mammalian evolution and lacks allelic polymorphism. 5-7 After activation, V␣14 NKT cells inhibit tumor metastasis in certain experimental animal models. 8 -10 Furthermore, i.v. injection of ␣-GalCer-pulsed DCs expressed a potent antitumor effect in a B16 melanoma liver metastasis model, where metastasized tumor nodules were eradicated. 11 Human NKT cells bearing the invariant V␣24J␣Q receptor are considered to be the counterpart of murine V␣14 NKT cells and may recognize antigens similar to those of murine V␣14 NKT cells because of striking homology between human V␣24 and mouse V␣14 receptors, particularly in their complementarity-determining region 3. 2 Indeed, human V␣24 NKT cells were activated by ␣-GalCer in a CD1d-dependent fashion 5,12,13 and showed strong antitumor activity upon ␣-GalCer stimulation. 14,15 Human V␣24 NKT cells play crucial roles in various immune responses, including antitumor and autoimmune responses. 16 -19 These reports demonstrated selective reduction in V␣24 NKT cell numbers. Little is known, however, about the nature of V␣24 NKT cells in primary lung cancer patients.We investigated the function of V␣24 NKT cells in peripheral blood and lung of patients with lung cancer. The numbers of V␣24 NKT cells were reduced, whereas the function of freshly isolated V␣24 NKT cells appeared to be preserved in tumor-bearing patients. Furthermore, the ability to present ␣-GalCer by patient DCs was within a normal range. Administration of ␣-GalCer-pulsed DCs expanded V␣14 NKT cells in the lung more than 10 ti...

show abstract

Extrathymic development of V alpha 14-positive T cells.

Cited by 130 publications

References 30 publications

Regulation of NKT Cells by Ly49: Analysis of Primary NKT Cells and Generation of NKT Cell Line

Regulation of NKT Cells by Ly49: Analysis of Primary NKT Cells and Generation of NKT Cell Line

Differential Regulation of Th1 and Th2 Functions of NKT Cells by CD28 and CD40 Costimulatory Pathways

Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients

Contact Info

Product

Resources

About