Characterisation of cellular and humoral autoimmune responses to histone H1 and core histones in human systemic lupus erythaematosus

2008 ◽  
Vol 68 (1) ◽  
pp. 110-116 ◽  
Author(s):  
G H Stummvoll ◽  
R D Fritsch ◽  
B Meyer ◽  
E Hoefler ◽  
M Aringer ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Cultures ◽  
Mononuclear Cells ◽  
Histone H1 ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
T Cell Clones ◽  
Cell Clones ◽  
Core Histones

Objective:To address key aspects of anti-histone autoimmunity in systemic lupus erythaematosus (SLE), we performed a detailed characterisation of cellular and humoral autoreactivity to histone H1 and the four core histones H2A, H2B, H3, H4 in patients with SLE and healthy controls.Methods:Peripheral blood mononuclear cells of 41 patients with SLE and 28 healthy controls were exposed to individual histones and proliferation was measured by [3H]-thymidine incorporation. H1-reactive T cell clones were obtained by limiting dilution. Cytokines and total IgG in culture supernatants was measured by ELISA, and autoantibodies to histones were determined by ELISA and immunoblotting.Results:Proliferative responses to H1 were more frequent and more pronounced in cell cultures from patients with SLE (p<0.002), while among the core histones only the response to H2A was increased in patient cultures (p<0.01). All histones elicited a Th1-like cytokine response in patients and controls (high interferon (IFN)γ and tumour necrosis factor (TNF)α, no interleukin (IL)4) with H1 inducing the highest levels of TNFα. However, H1 stimulated production of IgG and anti-histone antibodies only in cell cultures derived from patients with SLE. H1-specific T cell clones from patients and controls showed a CD4+CD28+ phenotype and a Th1 cytokine profile. Anti-histone antibodies were detected in 51% of patients with SLE, were primarily directed to H1, H3 and H4, and predominantly of the IgG2 subtype.Conclusions:Histone H1 constitutes a major B cell and T cell autoantigen in SLE, triggering a proinflammatory Th1 response and driving autoantibody production. This suggests that histone H1 may be of considerable relevance for the pathogenesis of SLE.

Cord blood mononuclear cells and milk-specific T-cell clones are tools to evaluate the residual immunogenicity of hydrolyzed milk formulas

1998 ◽  
Vol 101 (4) ◽  
pp. 514-520 ◽  
Author(s):  
Zsolt Szépfalusi ◽  
Ivo Nentwich ◽  
Eva Josta ◽  
Marianne Gerstmayra ◽  
Christof Ebner ◽  
...  
Keyword(s):  
T Cell ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
T Cell Clones ◽  
Cell Clones ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

The Characteristics of T Lymphocytic Clones Correlate with the Pathogenesis of Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1252-1252
Author(s):  
Ping Zhu ◽  
Xia Zhu ◽  
Xiao-ling Guo ◽  
Jiang-ying Gu ◽  
Yuan Ou
Keyword(s):  
T Cell ◽  
Size Distribution ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Healthy Controls ◽  
Thrombocytopenic Purpura ◽  
T Cell Clones ◽  
Average Value ◽  
Chronic Itp ◽  
Cell Clones ◽  
Acute Itp

Abstract Objective To determine the characteristics of T lymphocytic clones that correlate with the pathogenesis of idiopathic thrombocytopenic purpura (ITP) by investigating complementarity determining region (CDR3) repertoires of T cell receptors (TCRs) β chain variable region (BV). Methods Twenty-five of patients with idiopathic thrombocytopenic purpura (including 15 patients with acute ITP and 10 patients with chronic ITP), twenty of normal peoples and 20 of normal umbilical cord blood samples were enrolled. Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify 24 subfamily genes of TCR BV from peripheral blood lymphocytes of ITP patients and normal controls, the PCR products were run on denatured polyacrylamide sequencing gel, establishing spectratyping of TCR BV CDR3 gene expressing repertoire. The bands that dense or disappeared of TCR BV gene repertoire on the electrophoresis gel were used to analyze the variety of T cell clones in cases of ITP. The dense bands in the gel were cut down and sequencing. Compare with those major sequences of TCRBV gene in normal and abnormal T cell clones to understand the relationship among the TCRBV gene and ITP. Results: In acute ITP (aITP), the spectratyping of TCR BV CDR3 size distribution were similar to normal control (P=0.179), the oligoclonality could be observed with an average value of 2.73±0.88 per person in 15 cases of aITP. TCR BV CDR3 size distribution had little difference compared with aITP and healthy controls. Abnormal spectratyping of TCR BV CDR3 distribution could be observed significantly different between chronic ITP (cITP) patients and healthy controls (P&lt;0.05), with oligoclonality at an average value of 7.2±3.04 per person in 10 cases of cITP. Same T cell clone expansions could be observed in gene subfamilies of TCR BV8,BV13.1,BV14,BV17. In 10 of cITP patients, sequences could be read from 19 out of 20 dense bands on the gene spectratyping of TCR BV CDR3, which suggested some dominant T cell clones expanded in cITPs. In different patients of cITP, the expanded T cell clones shared identical or similar TCR BV gene or CDR3 encoded by the TCR BV gene. Two T cell clones in 2 patients had identical TCR BV8 gene sequences separately. Other 2 T cell clones in another 2 cITP patients had same TCR BV13.1. It showed those expanded T cell clones in the bodies of the cITP patients could recognize common antigen. The similar CDR3 was found in 2/4 expanded TCR BV17 T cell clones, with only 2 amino acids different in framework 4 (FR4). Two T cell clones had almost same sequence of CDR3 in TCR BV17 except for 4 basepairs difference in their full sequences. In analyzing the motifs in CDR3 of different cITPs, we found three common motifs (E/DTQYFGPG;N(K)EQFFGPG;GANVLTFGAG) which were separately used in different TCR BV CDR3 of 19 expanded T cell clones. Among these motifs, TCR BV of 7/19 T cell clones shared common E/DTQYFGPG;TCR BV of 4/19 T cell clones shared common N(K)EQFFGPG; TCR BV17 of 3/4 T cell clones had common GANVLTFGAG. Compared with the various sequence of 10 T cell clones in 6 cases of SLE patients that we had reported (Journal of Chinese Medicine2003;83(10):1648–1652), 5/10 T cell clones of the SLEs shared the motif NEQFFGPG in the CDR3.Three of TCR BV13.1 in these T cell clones showed motif DTQYFGPG. Conclusion the cITPs have some abnormal expanded T cell clones that correlate with the pathogenesis, while aITPs have no significant expanded clones. All the cITP patients share 3 common motifs in TCR BV CDR3, which is possibly to recognize similar autoantigens.

scholarly journals Early Emergence and Long-Term Persistence of HIV-Infected T Cell Clones in Children

2020 ◽  
Author(s):  
Michael J. Bale ◽  
Mary Grace Katusiime ◽  
Daria Wells ◽  
Xiaolin Wu ◽  
Jonathan Spindler ◽  
...  
Keyword(s):  
T Cell ◽  
Infected Cell ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Peripheral Blood Mononuclear ◽  
T Cell Clones ◽  
Cell Clones ◽  
Integration Sites ◽  
Infected Cells

AbstractLittle is known about the emergence and persistence of HIV-infected T cell clones in perinatally-infected children. We analyzed peripheral blood mononuclear cells for clonal expansion in 11 children who initiated antiretroviral therapy (ART) between 1.8-17.4 months of age and with viremia suppressed for 6-9 years. We obtained 8,662 HIV-1 integration sites from pre-ART and 1,861 sites on ART. Expanded clones of infected cells were detected pre-ART in 10/11 children. In 8 children, infected cell clones detected pre-ART persisted for 6-9 years on ART. A comparison of integration sites in the samples obtained on ART with healthy donor PBMC infected ex-vivo showed selection for cells with proviruses integrated in BACH2 and STAT5B. Our analyses indicate that, despite marked differences in T cell composition and dynamics between children and adults, HIV-infected cell clones are established early in children, persist for up to 9 years on ART, and can be driven by proviral integration in proto-oncogenes.

scholarly journals Evolution of retrovirus-infected premalignant T-cell clones prior to adult T-cell leukemia/lymphoma diagnosis

Blood ◽  
2020 ◽  
Vol 135 (23) ◽  
pp. 2023-2032 ◽  
Author(s):  
Aileen G. Rowan ◽  
Richard Dillon ◽  
Aviva Witkover ◽  
Anat Melamed ◽  
Maria-Antonietta Demontis ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Driver Mutations ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
T Cell Clones ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Cell Clones

Abstract Adult T-cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targeted sequencing to track the evolution of the malignant clone in 6 individuals, 2 to 10 years before the diagnosis of ATL. Clones of premalignant HTLV-1–infected cells bearing known driver mutations were detected in the blood up to 10 years before individuals developed acute and lymphoma subtype ATL. Six months before diagnosis, the total number and variant allele fraction of mutations increased in the blood. Peripheral blood mononuclear cells from premalignant cases (1 year prediagnosis) had significantly higher mutational burden in genes frequently mutated in ATL than did high-risk, age-matched HTLV-1 carriers who remained ATL-free after a median of 10 years of follow-up. These data show that HTLV-1–infected T-cell clones carrying key oncogenic driver mutations can be detected in cases of ATL years before the onset of symptoms. Early detection of such mutations may enable earlier and more effective intervention to prevent the development of ATL.

Antileukemic HLA-Restricted T-Cell Clones Generated With Naturally Processed Peptides Eluted From Acute Myeloblastic Leukemia Blasts

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Marina Ostankovitch ◽  
Agnès Buzyn ◽  
Delphine Bonhomme ◽  
Francine Connan ◽  
Didier Bouscary ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Acute Myeloblastic Leukemia ◽  
Peripheral Blood Mononuclear ◽  
T Cell Clones ◽  
Cell Clones ◽  
B7 Molecules ◽  
Blast Cells

Recent studies have shown that transfusions of HLA-compatible donor lymphocytes may induce complete remission in marrow-grafted patients with relapses of acute myeloblastic leukemia (AML). We investigated the in vitro generation of antileukemia T-cell clones obtained from the peripheral blood mononuclear cells of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the leukemic blasts) after stimulation with a pool of naturally processed peptides extracted from leukemic blast cells collected at diagnosis from a patient with hyperleucocytosis AML. We recovered a significant quantity of peptides that bound to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte (CTL) lines and clones specific for the eluted AML peptides and restricted to the HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic cells, and one clone was able to interact with the leukemic blasts from which the naturally processed peptides had been eluted. Such T-cell clones might provide a rationale for the development of adoptive immunotherapy and could be used to improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft-versus-leukemia response in patients with AML.

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