A CD2-Green Fluorescence Protein-Transgenic Mouse Reveals Very Late Antigen-4-Dependent CD8+ Lymphocyte Rolling in Inflamed Venules

Singbartl, Kai; Thatte, Jayant; Smith, Michael L.; Wethmar, Klaus; Day, Kathleen; Ley, Klaus

doi:10.4049/jimmunol.166.12.7520

Cited by 63 publications

(34 citation statements)

References 39 publications

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“…For example, T cells with a CD2 promoter driving GFP expression allowed visualization of T cell rolling and adhesion in postcapillary venules during inflammation in vivo (20). Transgenic GFP- The present study shows that HT-1080-dual-color cells are useful for visualization of cellular and nuclear dynamics in vivo.…”

Section: Discussionmentioning

confidence: 96%

Real-time In vivo Dual-color Imaging of Intracapillary Cancer Cell and Nucleus Deformation and Migration

Yamauchi

Yang²,

Jiang³

et al. 2005

Cancer Research

156

128

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The mechanism of cancer cell deformation and migration in narrow vessels is incompletely understood. In order to visualize the cytoplasmic and nuclear dynamics of cells migrating in capillaries, red fluorescent protein was expressed in the cytoplasm, and green fluorescent protein, linked to histone H2B, was expressed in the nucleus of cancer cells. Immediately after the cells were injected in the heart of nude mice, a skin flap on the abdomen was made. With a color CCD camera, we could observe highly elongated cancer cells and nuclei in capillaries in the skin flap in living mice. The migration velocities of the cancer cells in the capillaries were measured by capturing images of the dual-color fluorescent cells over time. The cells and nuclei in the capillaries elongated to fit the width of these vessels. The average length of the major axis of the cancer cells in the capillaries increased to approximately four times their normal length. The nuclei increased their length 1.6 times in the capillaries. Cancer cells in capillaries over 8 Mm in diameter could migrate up to 48.3 Mm/hour. The data suggests that the minimum diameter of capillaries where cancer cells are able to migrate is approximately 8 Mm. The use of the dual-color cancer cells differentially labeled in the cytoplasm and nucleus and associated fluorescent imaging provide a powerful tool to understand the mechanism of cancer cell migration and deformation in small vessels. (Cancer Res 2005; 65(10): 4246-52)

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Section: Discussionmentioning

confidence: 96%

Real-time In vivo Dual-color Imaging of Intracapillary Cancer Cell and Nucleus Deformation and Migration

Yamauchi

Yang²,

Jiang³

et al. 2005

Cancer Research

156

128

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“…Taking the findings in earlier studies and the transgene analysis into account, the phenotypic difference between T-bet tg/wt and T-bet tg/tg likely reflects the difference in T-bet expression levels in T cells. 35,36 Moreover, we were able to rule out the possible disruption of gene regulatory sequences due to the transgene homozygosity, as PAP development was observed in the other transgenic lines.…”

Section: Discussionmentioning

confidence: 98%

T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung

Iriguchi

Kikuchi

Kaneko

et al. 2015

Blood

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Key Points• Mice overexpressing T-bet in T cells show aberrant hematopoiesis of myeloid cells and functional conversion of regional macrophages.• The mice developed a severe PAP-like disease with a hematopoietic disorder resembling the human disease.Although overexpression of T-bet, a master transcription factor in type-1 helper T lymphocytes, has been reported in several hematologic and immune diseases, its role in their pathogenesis is not fully understood. In the present study, we used transgenic model mice (T-bet tg/wt and T-bet tg/tg ) to investigate the effects of T-bet overexpression selectively in T lymphocytes on the development of hematologic and immune diseases. The results showed that T-bet overexpression in T cells spontaneously induced maturation arrest in the mononuclear phagocyte lineage, as well as spontaneous dermatitis and pulmonary alveolar proteinosis (PAP)-like disease in T-bet tg/wt and T-bet tg/tg mice, respectively. T-bet tg/tg alveoli with the PAP phenotype showed remarkable reorganization of alveolar mononuclear phagocyte subpopulations and impaired function, in addition to augmented T-cell infiltration. In addition, PAP development in T-bet tg/tg mice was found to be associated with increased migration of myeloid cells from the bone marrow into the peripheral blood. These findings reveal an unexpected link between T-bet overexpression in T lymphocytes and the development of PAP caused by reorganization of mononuclear phagocytes in the lung, and provide new insight into the molecular pathogenesis of secondary PAP accompanied by hematologic disorders. (Blood. 2015;125(2):370-382)

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“…This discrepancy could be due to variation in HCV core expression, as most other core TG-mouse lines direct the transcription of core protein to hepatocytes. The expression of genes under the control of the CD2 promoter have been detected in T cells (21,54,67) (9,10,51), the HCV core-induced immune dysregulation may depend for its intracellular expression on immune cells rather than hepatocytes. Furthermore, the magnitude of allogeneic responses in CBA (H-2 k ) versus BALB/c (H-2 d ) mice was similar to that in C57BL/6 (H-2 b ) versus BALB/c (H-2 d ) mice (24).…”

Section: Discussionmentioning

confidence: 99%

“…The expression plasmid contains the 5-kb CD2 promoter and the 5.5-kb locus control region of the human CD2 gene (67). The CD2 promoter has been shown to direct T-cell expression of a desired gene in a position-independent and copy number-dependent manner (54,67).…”

Section: Generation Of Core Tg Mouse Linesmentioning

confidence: 99%

Hepatitis C Virus Core Protein Leads to Immune Suppression and Liver Damage in a Transgenic Murine Model

Soguero

Joo

Chianese‐Bullock

et al. 2002

J Virol

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Hepatitis C virus (HCV) is remarkably efficient in establishing persistent infection, possibly mediated by an impaired immune response to HCV infection. There is compelling evidence that HCV can infect immune cells, such as macrophages, B cells, and T cells. It has been previously reported that HCV core, the first protein expressed during the early phase of viral infection, contains the immunomodulatory function of suppressing host immune responses. This altered function of immune cells caused by HCV infection may explain the ineffective immune response to HCV. To further characterize the immunomodulatory role of HCV core in vivo, we generated transgenic (TG) mice by directing the expression of core protein to T lymphocytes by using the CD2 promoter. T-lymphocyte responses, including the production of gamma interferon and interleukin-2, were significantly diminished in these mice compared to their non-TG littermates. The inhibition of T-lymphocyte responsiveness may be due to the increased susceptibility of peripheral T lymphocytes to Fas-mediated apoptosis. Surprisingly, significant lymphocyte infiltration was observed in the portal tracts of livers isolated from core TG mice, associated with increasing serum alanine aminotransferase levels. Moreover, no intrahepatic lymphocytes or liver damage was found in non-TG littermates and core TG mice bred to Fas-deficient lpr mice. These results suggest that HCV core drives liver injury by increasing Fas-mediated apoptosis and liver infiltration of peripheral T cells.Hepatitis C virus (HCV) is a serious and growing worldwide threat to human health. It is the major etiologic agent of non-A, non-B hepatitis and infects an estimated 400 million people, more than 3% of the world population. One of the remarkable features of HCV infection is the high rate of viral persistence. More than 80% of HCV-infected individuals develop chronic disease, which can progress to liver cirrhosis and hepatocellular carcinoma. In addition to HCV replication in hepatocytes, immune cells, such as monocytes, B cells, and T cells, can also support viral replication (13,33,41), although studies of viral replication in the peripheral lymphocytes of HCV-infected patients have had conflicting results (8). The widespread cellular distribution of CD81 and low-density lipoprotein receptor, putative HCV receptors, is consistent with HCV binding to cells other than hepatocytes (2, 47). However, studies of HCV pathogenesis have been hampered by the lack of a small-animal model.

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A CD2-Green Fluorescence Protein-Transgenic Mouse Reveals Very Late Antigen-4-Dependent CD8+ Lymphocyte Rolling in Inflamed Venules

Cited by 63 publications

References 39 publications

Real-time In vivo Dual-color Imaging of Intracapillary Cancer Cell and Nucleus Deformation and Migration

Real-time In vivo Dual-color Imaging of Intracapillary Cancer Cell and Nucleus Deformation and Migration

T-cell–restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung

Hepatitis C Virus Core Protein Leads to Immune Suppression and Liver Damage in a Transgenic Murine Model

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