Dual Functions of Fractalkine/CX3C Ligand 1 in Trafficking of Perforin+/Granzyme B+ Cytotoxic Effector Lymphocytes That Are Defined by CX3CR1 Expression

Nishimura, Miyuki; Umehara, Hisanori; Nakayama, Takashi; Yoneda, Osamu; Hieshima, Kunio; Kakizaki, Mayumi; Dohmae, Naochika; Yoshie, Osamu; Imai, Toshio

doi:10.4049/jimmunol.168.12.6173

Cited by 297 publications

(285 citation statements)

References 45 publications

Supporting

Mentioning

263

Contrasting

Order By: Relevance

“…The results suggested infiltration of neutrophils expressing CXCR1 and CXCR2 and other types of leukocytes expressing CCR5 in chronic gastritis. Notably, the signals of CX3CR1 were also frequently detected in gastritis tissues, suggesting infiltration of CX3CR1-expressing cytotoxic T cells, 22 although the expression of its ligand fractalkine/CX3CL1 was hardly detected.…”

Section: Rt-pcr Analysismentioning

confidence: 99%

Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis

Ohtani

Nakayama

et al. 2004

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

Chronic gastritis is frequently associated with infection of Helicobacter pylori and characterized by tissue infiltration of neutrophils, lymphocytes, and plasma cells. To address the mechanism of lymphocyte infiltration in chronic gastritis, we examined the expression of chemokines and their receptors using frozen sections of chronic gastritis, obtained from 23 patients who underwent gastrectomy for gastric cancer. By immuno histochemistry, lymphocytes in inflamed gastric mucosa expressed CCR5 abundantly, CXCR3 less frequently, and CCR4 sparsely. The numbers of CCR5 þ cells, which were composed of mainly CD8 þ and partly CD4 þ T cells, were positively correlated with the degree of neutrophil infiltration, and decreased in areas with intestinal metaplasia or mucosal atrophy. RANTES/CCL5, one of the ligands of CCR5, was localized mainly in CD8 þ and partly CD4 þ T cells with a characteristic dotted pattern, and such lymphocytes were most densely distributed around the neck region of gastric glands. In situ hybridization confirmed the expression of CCL5 mRNA in these cells, and immunoelectron microscopy revealed localization of CCL5 in the membrane-bound granules, which most probably corresponded to the cytolytic granules of cytotoxic T cells. The numbers of CCL5 þ lymphocytes showed a close correlation with the degree of neutrophil infiltration and markedly decreased in intestinal metaplasia. In conclusion, our data suggest that, together with neutrophils, CCL5 þ T cells, presumably activated cytotoxic T cells, would play important roles in the active inflammatory process of chronic gastritis. Our data also suggest a self-recruiting mechanism involving CCR5 and CCL5 for tissue accumulation of such T cells.

show abstract

Section: Rt-pcr Analysismentioning

confidence: 99%

Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis

Ohtani

Nakayama

et al. 2004

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

show abstract

“…1B). By using the pattern of expression of CD45RA, CD45RO, and CD27, human CD8 ϩ T cells can be further fractionated into four functional subsets: naive (CD45RA ϩ CD27 ϩ ), memory (CD45RO ϩ CD27 ϩ ), early effector (CD45RO ϩ CD27 Ϫ ), and terminally differentiated effector (CD45RA ϩ CD27 Ϫ ) (31,32). We therefore performed double staining of purified CD8 ϩ T cells for D3 and CD45RA or CD45RO, and of purified CD45RA ϩ CD8 ϩ T cells for D3 and CD27.…”

Section: Selective Expression Of D3 In Naive Cd8 ϩ T Cellsmentioning

confidence: 99%

Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells via Dopamine Receptor D3

Watanabe

Nakayama

Nagakubo

et al. 2006

The Journal of Immunology

Self Cite

122

158

View full text Add to dashboard Cite

The nervous systems affect immune functions by releasing neurohormones and neurotransmitters. A neurotransmitter dopamine signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. The secondary lymphoid tissues are highly innervated by sympathetic nerve fibers that store dopamine at high contents. Lymphocytes also produce dopamine. In this study, we examined expression and function of dopamine receptors in lymphocytes. We found that D3 was the predominant subtype of dopamine receptors in the secondary lymphoid tissues and selectively expressed by naive CD8+ T cells of both humans and mice. Dopamine induced calcium flux and chemotaxis in mouse L1.2 cells stably expressing human D3. These responses were almost completely inhibited by pertussis toxin, indicating that D3 was coupled with the Gαi class of G proteins. Consistently, dopamine selectively induced chemotactic responses in naive CD8+ T cells of both humans and mice in a manner sensitive to pertussis toxin and D3 antagonists. Dopamine was highly synergistic with CCL19, CCL21, and CXCL12 in induction of chemotaxis in naive CD8+ T cells. Dopamine selectively induced adhesion of naive CD8+ T cells to fibronectin and ICAM-1 through activation of integrins. Intraperitoneal injection of mice with dopamine selectively attracted naive CD8+ T cells into the peritoneal cavity. Treatment of mice with a D3 antagonist U-99194A selectively reduced homing of naive CD8+ T cells into lymph nodes. Collectively, naive CD8+ T cells selectively express D3 in both humans and mice, and dopamine plays a significant role in migration and homing of naive CD8+ T cells via D3.

show abstract

“…Recent studies have suggested that the interaction of CX3CL1 and CX3CR1 contributes to firm adhesion of leukocytes to endothelial cells (7). Furthermore, CX3CR1 defines circulating effector-killer lymphocytes and modulates their trafficking (8).…”

mentioning

confidence: 99%

Migration of CX3CR1‐positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis

Nanki¹,

Imai²,

Nagasaka³

et al. 2002

Arthritis & Rheumatism

Self Cite

130

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis (RA) is characterized by chronic inflammation of multiple joints. Large numbers of T cells, which produce type 1 cytokines, infiltrate into RA synovium. Chemokines and chemokine receptors are considered to contribute to the T cell infiltration. In this study, we examined the role of CX3CL1/fractalkine and its receptor CX3C chemokine receptor 1 (CX3CR1) in the T cell migration into RA synovium.Methods. Using flow cytometry, immunohistochemistry, and reverse transcription-polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA. Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry.Results. CX3CR1 expression by peripheral CD4؉ and CD8؉ T cells was up-regulated in RA patients. The peripheral CD4؉ and CD8؉ T cells expressing CX3CR1 predominantly produced interferon-␥ and tumor necrosis factor ␣, and expressed cytotoxic molecules such as granzyme A and perforin. Furthermore, CX3CR1؉,CD3؉ T cells infiltrated into RA synovium. CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium.Conclusion. Our findings suggest that the interactions of CX3CL1 and CX3CR1 might contribute to the accumulation of CX3CR1؉ T cells expressing type 1 cytokines and possessing cytotoxic granules in RA synovium.

show abstract

Dual Functions of Fractalkine/CX3C Ligand 1 in Trafficking of Perforin+/Granzyme B+ Cytotoxic Effector Lymphocytes That Are Defined by CX3CR1 Expression

Cited by 297 publications

References 45 publications

Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis

Infiltration of CD8+ T cells containing RANTES/CCL5+ cytoplasmic granules in actively inflammatory lesions of human chronic gastritis

Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells via Dopamine Receptor D3

Migration of CX3CR1‐positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis

Contact Info

Product

Resources

About