Faculty Opinions recommendation of A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage.

Distinct DNA methylation signatures, related to different prognosis, have been observed across many cancers, including T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological neoplasm. By global methylation analysis, two major phenotypes might be observed in T-ALL: hypermethylation related to better outcome and hypomethylation, which is a candidate marker of poor prognosis. Moreover, DNA methylation holds more than a clinical meaning. It reflects the replicative history of leukemic cells and most likely different mechanisms underlying leukemia development in these T-ALL subtypes. The elucidation of the mechanisms and aberrations specific to (epi-)genomic subtypes might pave the way towards predictive diagnostics and precision medicine in T-ALL. We present the current state of knowledge on the role of DNA methylation in T-ALL. We describe the involvement of DNA methylation in normal hematopoiesis and T-cell development, focusing on epigenetic aberrations contributing to this leukemia. We further review the research investigating distinct methylation phenotypes in T-ALL, related to different outcomes, pointing to the most recent research aimed to unravel the biological mechanisms behind differential methylation. We highlight how technological advancements facilitated broadening the perspective of the investigation into DNA methylation and how this has changed our understanding of the roles of this epigenetic modification in T-ALL.

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A brief history of T cell help to B cells

Nature Reviews Immunology ◽

10.1038/nri3803 ◽

2015 ◽

Vol 15 (3) ◽

pp. 185-189 ◽

Cited By ~ 238

Author(s):

Shane Crotty

Keyword(s):

T Cell ◽

B Cells ◽

History Of ◽

T Cell Help

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TRMmaintenance is regulated by tissue damage via P2RX7

Science Immunology ◽

10.1126/sciimmunol.aau1022 ◽

2018 ◽

Vol 3 (30) ◽

pp. eaau1022 ◽

Cited By ~ 33

Author(s):

Regina Stark ◽

Thomas H. Wesselink ◽

Felix M. Behr ◽

Natasja A. M. Kragten ◽

Ramon Arens ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

Tissue Damage ◽

Extracellular Nucleotides ◽

Critical Pathway ◽

Rna Profiling ◽

Molecular Pattern ◽

History Of ◽

Circulating T Cells

Tissue-resident memory T cells (TRM) are noncirculating immune cells that contribute to the first line of local defense against reinfections. Their location at hotspots of pathogen encounter frequently exposes TRM to tissue damage. This history of danger-signal exposure is an important aspect of TRM-mediated immunity that has been overlooked so far. RNA profiling revealed that TRM from liver and small intestine express P2RX7, a damage/danger-associated molecular pattern (DAMP) receptor that is triggered by extracellular nucleotides (ATP, NAD+). We confirmed that P2RX7 protein was expressed in CD8+ TRM but not in circulating T cells (TCIRC) across different infection models. Tissue damage induced during routine isolation of liver lymphocytes led to P2RX7 activation and resulted in selective cell death of TRM. P2RX7 activation in vivo by exogenous NAD+ led to a specific depletion of TRM while retaining TCIRC. The effect was absent in P2RX7-deficient mice and after P2RX7 blockade. TCR triggering down-regulated P2RX7 expression and made TRM resistant to NAD-induced cell death. Physiological triggering of P2RX7 by sterile tissue damage during acetaminophen-induced liver injury led to a loss of previously acquired pathogen-specific local TRM in wild-type but not in P2RX7 KO T cells. Our results highlight P2RX7-mediated signaling as a critical pathway for the regulation of TRM maintenance. Extracellular nucleotides released during infection and tissue damage could deplete TRM locally and free niches for new and infection-relevant specificities. This suggests that the recognition of tissue damage promotes persistence of antigen-specific over bystander TRM in the tissue niche.

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Arterial Thrombosis and Gangrene Secondary to Arachnidism

Vascular ◽

10.2310/6670.2009.00022 ◽

2009 ◽

Vol 17 (4) ◽

pp. 239-242

Author(s):

Jan M. Eckermann ◽

Theodore H. Teruya ◽

Christian Bianchi ◽

Ahmed M. Abou-Zamzam

Keyword(s):

Case Report ◽

Lower Extremity ◽

Vascular Disease ◽

Tissue Damage ◽

Arterial Thrombosis ◽

Progressive Necrosis ◽

Life Threatening ◽

History Of ◽

Spider Bites ◽

Spider Bite

Spider bites can cause local tissue damage as well as life-threatening complications. This is a case report of a female with no history of lower extremity vascular disease who presented with a spider bite on the dorsum of her foot. She developed progressive necrosis and eventually suffered limb loss despite attempts at revascularization.

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Enteropathy associated T-cell lymphoma

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0702080b ◽

2007 ◽

Vol 135 (1-2) ◽

pp. 80-84

Author(s):

Milena Bakrac ◽

Branka Bonaci-Nikolic ◽

Natasa Colovic ◽

Sanja Simic-Ogrizovic ◽

Miodrag Krstic ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Previous History ◽

Lymph Node Biopsy ◽

Intestinal Wall ◽

T Cell Lymphoma ◽

The Third ◽

History Of ◽

Small Intestinal ◽

Mesenterial Lymph Node

Enteropathy associated T-cell lymphoma (EATCL) is a high grade, pleomorphic peripheral T-cell lymphoma with usually cytotoxic phenotype. This is a case report of three patients with EATCL. The first patient was 50 year-old woman with four year history of gluten sensitive enteropathy (GSE). Diagnosis of lymphoma was confirmed after the resection of the jejunum (small intestine obstruction). Pathohistological (PAS, Reticulin, Giemsa) and immunohistochemical (anti-LCA, anti-CD20, anti- CD45RO, anti-CD3) methods revealed the diagnosis of EATCL: CD45RO+, CD3+. After the third cycle of chemotherapy, the disease progressed with massive lung infiltration. Patient died due to complications of bone marrow aplasia. The second patient was 23 year-old woman with long earlier history of GSE. She presented with the acute renal failure. According to established diagnosis of tubulointerstitial nephritis, she was treated with pulse doses of steroid therapy. After temporary improvement, she had dissemination of the disease. On MRI, small intestinal wall was thickened, and abdominal lymph nodes were enlarged with extraluminal compression of common bile duct. Laparotomy with mesenterial lymph node biopsy and consecutive pathohistological and immunohistochemical analyses revealed the diagnosis of EATCL. The patient received chemotherapy, but she died with signs of pulmonary embolization. The third patient was 53 year-old woman without previous history of GSE. Diagnosis of EATCL was revealed after the resection of jejunum because of small intestinal obstruction. She received two cycles of chemotherapy, but she died with signs of disease progression. IgA antiendomysial antibodies were detected in the serum of all patients. The overall survival of patients was 7 months. The possibility of lymphoma rising in patients with clinical progression of GSE despite gluten free diet must be kept in mind.

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The Evolutionary History of the Chymase Locus -a Locus Encoding Several of the Major Hematopoietic Serine Proteases

International Journal of Molecular Sciences ◽

10.3390/ijms222010975 ◽

2021 ◽

Vol 22 (20) ◽

pp. 10975

Author(s):

Srinivas Akula ◽

Zhirong Fu ◽

Sara Wernersson ◽

Lars Hellman

Keyword(s):

Mast Cell ◽

T Cell ◽

Serine Proteases ◽

Phylogenetic Trees ◽

Granzyme B ◽

Large Family ◽

Cathepsin G ◽

Immune Functions ◽

New Class ◽

History Of

Several hematopoietic cells of the immune system store large amounts of proteases in cytoplasmic granules. The absolute majority of these proteases belong to the large family of chymotrypsin-related serine proteases. The chymase locus is one of four loci encoding these granule-associated serine proteases in mammals. The chymase locus encodes only four genes in primates, (1) the gene for a mast-cell-specific chymotryptic enzyme, the chymase; (2) a T-cell-expressed asp-ase, granzyme B; (3) a neutrophil-expressed chymotryptic enzyme, cathepsin G; and (4) a T-cell-expressed chymotryptic enzyme named granzyme H. Interestingly, this locus has experienced a number of quite dramatic expansions during mammalian evolution. This is illustrated by the very large number of functional protease genes found in the chymase locus of mice (15 genes) and rats (18 genes). A separate expansion has also occurred in ruminants, where we find a new class of protease genes, the duodenases, which are expressed in the intestinal region. In contrast, the opossum has only two functional genes in this locus, the mast cell (MC) chymase and granzyme B. This low number of genes may be the result of an inversion, which may have hindered unequal crossing over, a mechanism which may have been a major factor in the expansion within the rodent lineage. The chymase locus can be traced back to early tetrapods as genes that cluster with the mammalian genes in phylogenetic trees can be found in frogs, alligators and turtles, but appear to have been lost in birds. We here present the collected data concerning the evolution of this rapidly evolving locus, and how these changes in gene numbers and specificities may have affected the immune functions in the various tetrapod species.

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Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion

Journal of Experimental Medicine ◽

10.1084/jem.20060964 ◽

2007 ◽

Vol 204 (3) ◽

pp. 645-655 ◽

Cited By ~ 181

Author(s):

Menno C. van Zelm ◽

Tomasz Szczepański ◽

Mirjam van der Burg ◽

Jacques J.M. van Dongen

Keyword(s):

Cell Proliferation ◽

T Cell ◽

B Cell ◽

B Lymphocytes ◽

Cell Expansion ◽

B Lymphocyte ◽

Somatic Hypermutation ◽

Homeostatic Proliferation ◽

History Of ◽

Lymphocyte Homeostasis

The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.

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