Lymphotactin: a Cytokine that Represents a New Class of Chemokine

Kelner, Gregory S.; Kennedy, Jacqueline; Bacon, Kevin B.; Kleyensteuber, Sarah; Largaespada, David A.; Jenkins, Nancy A.; Copeland, Neal G.; Bazán, J. Fernando; Moore, Kevin W.; Schall, Thomas J.; Zlotnik, Albert

doi:10.1126/science.7973732

Cited by 600 publications

(369 citation statements)

References 17 publications

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“…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%

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: Discussionmentioning

confidence: 99%

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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“…15,16 Lymphotactin (Lptn) is a C chemokine that specifically regulates the migration of T cells and NK cells. [17][18][19][20] Dilloo et al 21 reported that cotransfection of Lptn and interleukin-2 (IL-2) genes into tumor tissue could induce potent antitumor immunity through an attraction-expansion approach. We have also found that Lptn gene-modified DC could deliver MHC I-restricted tumor antigen peptide more efficiently to induce antitumor immunity in the 3LL Lewis lung carcinoma model.…”

Section: Ance To Tumor Challenge Most Effectively It Was Found That mentioning

confidence: 99%

“…Ex vivo experiments have suggested that the Lptn is particularly important for the recruitment of T cells and NK cells to the site of an immune response. [17][18][19][20] Therefore, the cotransfection of Lptn and TAA gene into DC may have the potential to overcome the above limitation and may be a promising approach to improve the therapeutic efficacy of DC-based tumor vaccines. Many studies showed that DC could attract T cells by secreting chemokines.…”

Section: Gene Therapymentioning

confidence: 99%

Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100

et al. 2002

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Lymphotactin (Lptn) is a C chemokine that attracts T cells and NK cells. Dendritic cells (DC) are highly efficient, specialized antigen-presenting cells and antigen-pulsed DC has been regarded as promising vaccines in cancer immunotherapy. The aim of our present study is to improve the therapeutic efficacy of DC-based tumor vaccine by increasing the preferential chemotaxis of DC to T cells. In this study, Lptnand/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model.

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“…Lymphotactin belongs to the chemokine group 38-40 that is regulated by proinflammatory or infectious stimuli, and was shown to be expressed mainly in activated T and Natural Killer (NK) cells. 41,42 The human Lymphotactin is implicated in allograft rejection, inflammatory bowel diseases and other immune system related diseases. 43 In general, chemokines stimulate cells of the immune system through activating specific G protein-coupled receptors (GPCRs).…”

Section: Introductionmentioning

confidence: 99%

Effects of Temperature and Salt Concentration on the Structural Stability of Human Lymphotactin: Insights from Molecular Simulations

Formaneck

Cui

2006

J. Am. Chem. Soc.

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Extensive molecular dynamics (MD) simulations (∼ 70 ns total) with explicit solvent molecules and salt ions are carried out to probe the effects of temperature and salt concentration on the structural stability of the human Lymphotactin (hLtn). The distribution of ions near the protein surface and the stability of various structural motifs are observed to exhibit interesting dependence on the local sequence and structure. Whereas chloride association to the protein is overall enhanced as the temperature increases, the sodium distribution in the C-terminal helical region and, to a smaller degree, the chloride distribution in the same region are found higher at the lower temperature. The similar trend is also observed in non-linear Poisson-Boltzmann calculations with a temperaturedependent water dielectric constant, once conformational averaging over a series of MD snapshots is done. The unexpected temperature dependence in the ion distribution is explained based on the cancellation of association entropy for ion-sidechain pairs of opposite-charge and like-charge characters, which have positive and negative contributions, respectively. The C-terminal helix is observed to partially melt while a short • strand forms at the higher temperature with little salt dependence. The N-termal region, by contrast, develops partial helical structure at a higher salt concentration. These observed behaviors are consistent with solvent and salt screening playing an important role in stabilizing the canonical chemokine fold of hLtn.

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Lymphotactin: a Cytokine that Represents a New Class of Chemokine

Cited by 600 publications

References 17 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

Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100

Effects of Temperature and Salt Concentration on the Structural Stability of Human Lymphotactin: Insights from Molecular Simulations

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