scholarly journals CD3delta deficiency arrests development of the alpha beta but not the gamma delta T cell lineage

1997 ◽  
Vol 16 (6) ◽  
pp. 1360-1370 ◽  
Author(s):  
V. P. Dave
Keyword(s):  
T Cell ◽  
Cell Lineage ◽  
Gamma Delta ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Signals involved in gamma/delta T cell versus alpha/beta T cell lineage commitment

1999 ◽  
Vol 11 (4) ◽  
pp. 239-249 ◽  
Author(s):  
Adrian C. Hayday ◽  
Domingo F. Barber ◽  
Nataki Douglas ◽  
Eric S. Hoffman
Keyword(s):  
T Cell ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Gamma Delta ◽  
Alpha Beta ◽  
Gamma Delta T Cell ◽  
Cell Versus

scholarly journals A delta T-cell receptor deleting element transgenic reporter construct is rearranged in alpha beta but not gamma delta T-cell lineages.

1995 ◽  
Vol 15 (12) ◽  
pp. 7022-7031 ◽  
Author(s):  
J Shutter ◽  
J A Cain ◽  
S Ledbetter ◽  
M D Rogers ◽  
R D Hockett
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gamma Delta ◽  
Alpha Chain ◽  
Chain Locus ◽  
Discrete Population ◽  
Alpha Beta ◽  
Gamma Delta T Cell

T cells can be divided into two groups on the basis of the expression of either alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain locus lies within the larger TCR alpha chain locus, control of the utilization of these two receptors is important in T-cell development, specifically for determination of T-cell type: rearrangement of the alpha locus results in deletion of the delta coding segments and commitment to the alpha beta lineage. In the developing thymus, a relative site-specific recombination occurs by which the TCR delta chain gene segments are deleted. This deletion removes all D delta, J delta, and C delta genes and occurs on both alleles. This delta deletional mechanism is evolutionarily conserved between mice and humans. Transgenic mice which contain the human delta deleting elements and as much internal TCR delta chain coding sequence as possible without allowing the formation of a complete delta chain gene were developed. Several transgenic lines showing recombinations between deleting elements within the transgene were developed. These lines demonstrate that utilization of the delta deleting elements occurs in alpha beta T cells of the spleen and thymus. These recombinations are rare in the gamma delta population, indicating that the machinery for utilization of delta deleting elements is functional in alpha beta T cells but absent in gamma delta T cells. Furthermore, a discrete population of early thymocytes containing delta deleting element recombinations but not V alpha-to-J alpha rearrangements has been identified. These data are consistent with a model in which delta deletion contributes to the implementation of a signal by which the TCR alpha chain locus is rearranged and expressed and thus becomes an alpha beta T cell.

scholarly journals Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-alpha/beta+ T cells and expansion of NK1.1+ TCR-gamma/delta+ T cell development in CD3 zeta-deficient mice.

1995 ◽  
Vol 182 (3) ◽  
pp. 891-895 ◽  
Author(s):  
H Arase ◽  
S Ono ◽  
N Arase ◽  
S Y Park ◽  
K Wakizaka ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Receptor ◽  
Gamma Delta ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Alpha Beta ◽  
Gamma Delta T Cell ◽  
Deficient Mice

The relationship between the structure of the T cell antigen receptor (TCR)-CD3 complex and development of NK1.1+ T cells was investigated. The TCR complex of freshly isolated NK1.1+ TCR-alpha/beta+ thymocytes contained CD3 zeta homodimers and CD zeta-FcR gamma heterodimers, whereas that of the majority of NK1.1- T cells did not contain FcR gamma. The function of CD3 zeta and FcR gamma in the development of NK1.1+ T cells was determined by analyzing CD3 zeta- and FcR gamma-deficient mice. The NK1.1+ T cells from wild-type and CD3 zeta-deficient mice had equal levels of CD3 expression. However, the development of NK1.1+ TCR-alpha/beta+ T cells was almost completely disrupted in thymus and spleen in CD3 zeta-deficient mice, whereas no alteration was observed in FcR gamma-deficient mice. In contrast, the number of novel NK1.1+ TCR-gamma/delta+ thymocytes expressing a surface phenotype similar to NK1.1+ TCR-alpha/beta+ thymocytes increased approximately six times in CD3 zeta-deficient mice. These findings establish the distinct roles of the CD3 zeta chain in the development of the following different thymic T cell compartments: NK1.1- TCR+, NK1.1+ TCR-alpha/beta+, and NK1.1+ TCR-gamma/delta+ thymocytes, which cannot be replaced by CD3 eta or FcR gamma chains.

scholarly journals Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells.

1993 ◽  
Vol 178 (3) ◽  
pp. 985-996 ◽  
Author(s):  
M J Skeen ◽  
H K Ziegler
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
T Cell Subsets ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Accessory Cells ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Peritoneal gamma/delta T cells from Listeria-immune mice show an enhanced potential to expand when restimulated with antigens or mitogens in vitro (see companion paper [Skeen, M. J., and H. K. Ziegler. 1993. J. Exp. Med. 178:971]). When cocultured with peritoneal alpha/beta T cells, the gamma/delta T cell population expanded preferentially even when the in vitro stimulus was specific for the alpha/beta T cell population. Purified gamma/delta T cells did not respond to alpha/beta T cell-specific stimuli. If isolated T cell subsets were recombined in cell mixing experiments, the resulting proliferative response was greater than additive. Irradiated alpha/beta T cells could enhance the proliferation of responding gamma/delta T cells, but the effect was unidirectional; i.e., irradiated gamma/delta T cells did not stimulate responding gamma/delta T cells. This effect appeared to be cytokine mediated and did not require cell-cell contact. Both recombinant interleukin 2 (rIL-2) and rIL-7 could support the expansion of the gamma/delta T cells, while rIL-7 was only minimally stimulatory for the alpha/beta T cells. The magnitude of the response by gamma/delta T cells to rIL-7 exceeded the response to other in vitro stimuli, including immobilized anti-T cell receptor monoclonal antibody, and was 50-100-fold greater than the alpha/beta T cell response to IL-7. This unique sensitivity of gamma/delta T cells to IL-7 was strongly enhanced by the presence of accessory cells. These cells could be replaced by rIL-1, establishing a synergy for IL-1 and IL-7 as factors that could uniquely stimulate this gamma/delta T cell population. Isolated peritoneal gamma/delta T cells from Listeria-immune mice react to heat-killed Listeria preparations in the presence of macrophages accessory cells in a non-H-2-restricted manner. Considered collectively, these results suggest a potential mechanism by which gamma/delta T cells can predominate in epithelial tissues and at sites of infection.

scholarly journals Comparative Transcriptomics of Alpha-Beta Subcutaneous Panniculitis-like T-Cell Lymphoma and Primary Cutaneous Gamma Delta T-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-17
Author(s):  
Xing Li ◽  
Kevin J Severson ◽  
Meera H Patel ◽  
Caitlin M Brumfiel ◽  
Alysia Hughes ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Subcutaneous Adipose Tissue ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Gamma Delta ◽  
Hub Genes ◽  
Alpha Beta ◽  
Gamma Delta T Cell ◽  
Subcutaneous Adipose

Background: Subcutaneous lymphomas are a heterogeneous group of diseases with variable clinical behavior that ranges from a lymphoproliferative disorder to an aggressive cytotoxic lymphoma. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon, often indolent cutaneous lymphoma that localizes to the subcutaneous adipose tissue. These tumors exhibit an alpha/beta phenotype (abSPTCL). Primary cutaneous gamma-delta T-cell lymphoma (PCgdTCL) is a rare, highly aggressive lymphoma that frequently involves the subcutaneous adipose tissue. The goal of this study is to identify key inflammatory and oncogenic pathways in SPTCL and PCgdTCL to determine which mutational or expression patterns differentiate abSPTCL and PCgdTCL. A comprehensive catalog of cancer gene expression profiles generated via RNA sequencing on patient samples is essential to understand tumorigenesis and to develop effective therapies. Methods: We performed transcriptomic profiling analysis using RNA sequencing in lesional skin biopsies from patients of abSPTCL (n=10), PCgdTCL (n=9), and controls (n=5). Differential analyses were performed on the entire transcriptomic profiles among the 3 groups. Results: Although the transcriptomic profiles of abSPTCL and PCgdTCL samples had similarities, there were notable differences between these groups that may elucidate unique pathways that propagate each disease. In contrast to abSPTCL, PCgdTCL samples demonstrated upregulation of cell motility and proliferation, and downregulation of pathways involving apoptosis and tumor necrosis factor production. The most significantly upregulated gene pathways in both abSPTCL and PCgdTCL samples were those involving immune and inflammatory response, viral defense, type I interferon signaling, interferon-gamma-mediated signaling, and positive regulation of T cell proliferation. The most significantly downregulated gene pathways in the two groups were those involving cell adhesion, rRNA processing and translation, and extracellular matrix organization. The top 5 upregulated immune response and downregulated cell adhesion hub genes for abSPTCL highlighted by gene interaction network analysis included: TNF, CTLA4, CD86, IL10, CCR5 & ITGB5, ITGA8, VWF, APP, CDH5, respectively. Conclusion: Our transcriptomic profiling pinpoints disease-related enrichment pathways and gene functions in abSPTCL and PCgdTCL patients, which may shed light on molecular mechanisms that drive disease activity. Hub genes in abSPTCL represent potential drug targets for further development of novel therapies. Disclosures Mangold: Kirin:Membership on an entity's Board of Directors or advisory committees;Elorac:Research Funding;Sun Pharma:Research Funding;MiRagen:Research Funding;Solagenix:Research Funding.

Rare SOX13 Sequence Variations in Pediatric Idiopathic Thrombocytopenic Purpura Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3420-3420
Author(s):  
Johannes R Rischewski ◽  
Johanna Wyss ◽  
Sylvie Stocker ◽  
Martin Hergersberg ◽  
Andreas R Huber ◽  
...  
Keyword(s):  
T Cell ◽  
Control Sample ◽  
European Ancestry ◽  
Biliary Cirrhosis ◽  
Coding Region ◽  
Gamma Delta ◽  
Thrombocytopenic Purpura ◽  
Sequence Variations ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Abstract Introduction: Idiopathic or immune-thrombocytopenic purpura (ITP) is defined as a bleeding disorder with the hallmark of autoimmune mediated thrombocytopenia. ITP is a diagnosis of exclusion. Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver. Many nonhepatic autoimmune diseases are found in association with PBC, and may prompt initial presentation. Several case reports described the co-occurrence of ITP and PBC. In some PBC patients, autoantibodies against SOX13 can be detected. SOX13 has been identified as a transcription factor promoting gamma-delta T-cell development while opposing alpha-beta T cell differentiation. As ITP has been linked to the autoimmune bicytopenic Evans syndrome, which may present as autoimmune lymphoproliferative syndrome (ALPS) with the hallmark of increased alpha-beta double negative T-cells, we are interested in a potentially etiological role of molecular SOX13 sequence variations in ITP patients. Material and methods: After obtaining informed consent from ITP patients (n=34) and their legal guardians to participate in the IRB approved study genomic DNA was extracted from peripheral blood samples. The complete coding region of SOX13 including the classical non-coding splice sites was amplified by PCR. The amplicons were screened for sequence variations by Denaturing High Performance Liquid Chromatography (DHPLC) after heteroduplex induction. All samples with aberrant DHPLC retention patterns were directly sequenced. Results: Two rare heterozygous sequence variations in the coding region of SOX13 were detected in a total of 4 patients (12%): c.1603C>T (Pro534Ser) and c.1836 C>T (synonymous). Discussion: In a healthy cohort with European ancestry the heterozygous c.1603C>T (Pro534Ser) genotype was detected in 1.7% of individuals. In our cohort 6% of the ITP patients were heterozygous. 2.6% of individuals in a cohort of African-Americans and Caucasians carried the heterozygous genotype c.1836C>T (synonymous). 6% of the investigated ITP patients were heterozygous. A surprising high proportion (12%) of pediatric ITP patients carries one of two rare SOX13 sequence variations. The rare heterozygous genotypes are 3.5 (c.1603C>T) respectively 2.3 times (c.1836C>T) more common than in published non-ITP cohorts. Conclusion: It seems possible, that rare alleles of SOX13 accumulate in pediatric ITP cohorts. Larger case-control sample studies are needed to verify the results. The rare genotypes could influence the alpha-beta versus gamma-delta T-cell balance in the studied pediatric ITP patients. Immunological studies of our cohort are necessary to evaluate this suggested association.

scholarly journals Retroviral transformation in vitro of chicken T cells expressing either alpha/beta or gamma/delta T cell receptors by reticuloendotheliosis virus strain T.

1993 ◽  
Vol 177 (3) ◽  
pp. 647-656 ◽  
Author(s):  
M D Marmor ◽  
T Benatar ◽  
M J Ratcliffe
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Reticuloendotheliosis Virus ◽  
Spleen Cells ◽  
Gamma Delta ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Exposure of normal juvenile chicken bone marrow cells to the replication defective avian reticuloendotheliosis virus strain T (REV-T) (chicken syncytial virus [CSV]) in vitro resulted in the generation of transformed cell lines containing T cells. The transformed T cells derived from bone marrow included cells expressing either alpha/beta or gamma/delta T cell receptors (TCRs) in proportions roughly equivalent to the proportions of TCR-alpha/beta and TCR-gamma/delta T cells found in the normal bone marrow in vivo. Essentially all TCR-alpha/beta-expressing transformed bone marrow-derived T cells expressed CD8, whereas few, if any, expressed CD4. In contrast, among TCR-gamma/delta T cells, both CD8+ and CD8- cells were derived, all of which were CD4-. Exposure of ex vivo spleen cells to REV-T(CSV) yielded transformed polyclonal cell lines containing > 99% B cells. However, REV-T(CSV) infection of mitogen-activated spleen cells in vitro resulted in transformed populations containing predominantly T cells. This may be explained at least in part by in vitro activation resulting in dramatically increased levels of T cell REV-T(CSV) receptor expression. In contrast to REV-T(CSV)-transformed lines derived from normal bone marrow, transformed lines derived from activated spleen cells contained substantial numbers of CD4+ cells, all of which expressed TCR-alpha/beta. While transformed T cells derived from bone marrow were stable for extended periods of in vitro culture and were cloned from single cells, transformed T cells from activated spleen were not stable and could not be cloned. We have therefore dissociated the initial transformation of T cells with REV-T(CSV) from the requirements for long-term growth. These results provide the first demonstration of efficient in vitro transformation of chicken T lineage cells by REV-T(CSV). Since productive infection with REV-T(CSV) is not sufficient to promote long-term growth of transformed cells, these results further suggest that immortalization depends not only upon expression of the v-rel oncogene but also on intracellular factor(s) whose expression varies according to the state of T cell physiology and/or activation.

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