A molecular analysis of NKT cells: identification of a class-I restricted T cell-associated molecule (CRTAM)

Kennedy, Jacqueline; Vicari, Alain; Saylor, Vicki; Zurawski, Sandra; Copeland, Neal G.; Gilbert, Debra J.; Jenkins, Nancy A.; Zlotnik, Albert

doi:10.1002/jlb.67.5.725

Cited by 76 publications

(64 citation statements)

References 49 publications

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“…By a nonquantitative PCR assay, our data confirmed previous experiments (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and showed that the constitutive and activation-induced XCL1 message detected in PBMC was also present in both CD4 ϩ and CD8 ϩ lymphocytes. However, comparison of data obtained by conventional PCR (Fig.…”

Section: Discussionsupporting

confidence: 90%

“…Two major problems still need to be solved. Firstly, although the expression of XCL1 has been described virtually in all lymphocyte populations, including CD8 ϩ lymphocytes (7)(8)(9)(10)(11)(12), CD4 ϩ lymphocytes (19 -21), NK cells (7,13,14), and ␥␦ ϩ T cells (17,18) under a variety of experimental conditions, the available data are mostly based on nonquantitative PCR analyses, and no thorough comparison of the actual XCL1 synthesis and/or the expression in different T cell populations was attempted. Secondly, although clear XCL1 effects other than lymphocyte migration were described on several cell types, including CD4 ϩ T cells (22,57), this issue is as yet incompletely addressed, and the position of XCL1 within the cytokine/ chemokine network is still elusive.…”

Section: Discussionmentioning

confidence: 99%

“…First, the source of XCL1 within the immune system is still poorly defined. On the one hand, lymphotactin synthesis was originally described as strictly confined to CD8 ϩ T cells (8 -12); more recently, XCL1 expression was also reported in several other leukocyte populations, including NK cells (7,13,14), dendritic cells (15), activated mast cells (16), TCR ␥␦ ϩ T cells (17,18), and even CD4 ϩ T cells (19), especially those belonging to the Th1 subset (20,21). In most cases, however, no quantitative comparisons between different cell populations were performed, and the ability to produce XCL1 was mostly evaluated by nonquantitative PCR approaches.…”

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confidence: 99%

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CD8+αβ+ T Cells That Lack Surface CD5 Antigen Expression Are a Major Lymphotactin (XCL1) Source in Peripheral Blood Lymphocytes

Stievano

Tosello

Marcato

et al. 2003

The Journal of Immunology

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To better characterize the cellular source of lymphotactin (XCL1), we compared XCL1 expression in different lymphocyte subsets by real-time PCR. XCL1 was constitutively expressed in both PBMC and CD4+ cells, but its expression was almost 2 log higher in CD8+ cells. In vitro activation was associated with a substantial increase in XCL1 expression in both PBMC and CD8+ cells, but not in CD4+ lymphocytes. The preferential expression of XCL1 in CD8+ cells was confirmed by measuring XCL1 production in culture supernatants, and a good correlation was found between figures obtained by real-time PCR and XCL1 contents. XCL1 expression was mostly confined to a CD3+CD8+ subset not expressing CD5, where XCL1 expression equaled that shown by γδ+ T cells. Compared with the CD5+ counterpart, CD3+CD8+CD5− cells, which did not express CD5 following in vitro activation, showed preferential expression of the αα form of CD8 and a lower expression of molecules associated with a noncommitted/naive phenotype, such as CD62L. CD3+CD8+CD5− cells also expressed higher levels of the XCL1 receptor; in addition, although not differing from CD3+CD8+CD5+ cells in terms of the expression of most α- and β-chemokines, they showed higher expression of CCL3/macrophage inflammatory protein-1α. These data show that TCR αβ-expressing lymphocytes that lack CD5 expression are a major XCL1 source, and that the contribution to its synthesis by different TCR αβ-expressing T cell subsets, namely CD4+ lymphocytes, is negligible. In addition, they point to the CD3+CD8+CD5− population as a particular T cell subset within the CD8+ compartment, whose functional properties deserve further attention.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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CD8+αβ+ T Cells That Lack Surface CD5 Antigen Expression Are a Major Lymphotactin (XCL1) Source in Peripheral Blood Lymphocytes

Stievano

Tosello

Marcato

et al. 2003

The Journal of Immunology

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“…We previously identified class I-restricted T cell-associated molecule (CRTAM) as an activation-induced surface receptor predominantly expressed on CD8 ϩ T cells, and nectin-like molecule-2 (Necl2)/TSLC1/CADM1 as its ligand (11)(12)(13)(14). In this study, the physiological role of the CRTAM-Necl2 interaction was analyzed in CRTAM-deficient (CRTAM Ϫ/Ϫ ) mice.…”

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confidence: 99%

CRTAM Confers Late-Stage Activation of CD8+ T Cells to Regulate Retention within Lymph Node

Takeuchi

Itoh

Takumi

et al. 2009

The Journal of Immunology

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In vivo immune response is triggered in the lymph node, where lymphocytes for entry into, retention at, and migration to effector sites are dynamically regulated. The molecular mechanism underlying retention regulation is the key to elucidating in vivo regulation of immune response. In this study, we describe the function of the adhesion molecule class I-restricted T cell-associated molecule (CRTAM) in regulating CD8+ T cell retention within the lymph node and eventually effector function. We previously identified CRTAM as a receptor predominantly expressed on activated CD8+ T cells, and nectin-like molecule-2 (Necl2) as its ligand. In vivo function of CRTAM-Necl2 interaction was analyzed by generating CRTAM−/− mice. CRTAM−/− mice exhibited reduced protective immunity against viral infection and impaired autoimmune diabetes induction in vivo. Although Ag-specific CRTAM−/− CD8+ T cells showed normal CTL functions in vitro, their number in the draining lymph node was reduced. Because CRTAM+ T cells bound efficiently to Necl2-expressing CD8+ dendritic cells (DCs) that reside in T cell area of lymph node, CRTAM may induce retention by binding to CD8+ DCs at the late stage of activation before proliferation. The CRTAM-mediated late interaction with DCs induced retention of activated CD8+ T cells in an Ag-independent fashion, and this possibly resulted in effective CTL development in the draining lymph node.

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“…Our data showed that TCS upregulated the expression of the tumor suppressor gene TSLC1 on tumor cells, along with the expression of its ligand, CRTAM, on activated T cells. 31,32 Blocking TSLC1 expression with siRNA eliminated the effect of TCS on T cells. The interaction between TSLC1 and CRTAM may promote the proliferation of activated T cells and the secretion of IFNc thereby enhancing the anti-tumor effects of T cells.…”

Section: Cd8mentioning

confidence: 99%

Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM

et al. 2011

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Trichosanthin (TCS), extracted from the Chinese medicinal herb Trichosanthes kirilowi, has shown promise for the inhibition of tumor growth. However, its immunomodulatory effect on tumor-host interaction remains unknown. In this study, we focused on the effect of TCS on murine anti-tumor immune response in the 3LL Lewis lung carcinoma tumor model and explored the possible molecular pathways involved. In addition to inhibiting cell proliferation and inducing apoptosis in the 3LL tumor, TCS retarded tumor growth and prolonged mouse survival more significantly in C57BL/6 immunocompetent mice than in nude mice. This reflected the fact that the host immune system was involved in tumor eradication. Using FACS analysis, we found that TCS increased the percentage of effector T cells, particularly Interferon-gamma (IFN-c) producing CD41 and CD8 1 T cells from tumor-bearing mice. TCS also promoted the vigorous proliferation of antigen-specific effector T cells, markedly increased Th1 cytokine secretion and elicited more memory T cells in tumor-bearing mice, consequently enhancing the anti-tumor response and inducing immune protection. Furthermore, we found that TCS upregulated the expression of tumor suppressor in lung cancer 1 (TSLC1) in 3LL tumor cells and the expression of its ligand, class I-restricted T cell-associated molecule (CRTAM), in effector T cells. Blocking TSLC1 expression with small interfering RNA (siRNA) significantly eliminated the effects of TCS on the proliferation and cytokine secretion of effector T cells, suggesting that TCS enhances anti-tumor immune response at least partially by boosting the interaction between TSLC1 and CRTAM. Collectively, our data demonstrate that TCS not only affects tumor cells directly, but also enhances anti-tumor immunity via the interaction between TSLC1 and CRTAM. These findings may lead to the development of a novel approach for tumor regression.

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A molecular analysis of NKT cells: identification of a class-I restricted T cell-associated molecule (CRTAM)

Cited by 76 publications

References 49 publications

CD8+αβ+ T Cells That Lack Surface CD5 Antigen Expression Are a Major Lymphotactin (XCL1) Source in Peripheral Blood Lymphocytes

CD8+αβ+ T Cells That Lack Surface CD5 Antigen Expression Are a Major Lymphotactin (XCL1) Source in Peripheral Blood Lymphocytes

CRTAM Confers Late-Stage Activation of CD8+ T Cells to Regulate Retention within Lymph Node

Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM

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