scholarly journals UV irradiation can induce in vitro clonal anergy in alloreactive cytotoxic T lymphocytes

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 176-181 ◽  
Author(s):  
T Kobata ◽  
H Ikeda ◽  
Y Ohnishi ◽  
N Urushibara ◽  
TA Takahashi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Calcium Ionophore ◽  
Target Cells ◽  
Ionophore A23187 ◽  
Peripheral Blood Mononuclear ◽  
High Affinity ◽  
Clonal Anergy

The alloreactive cytotoxic T lymphocytes (CTL) were generated by coculturing peripheral blood mononuclear cells (PBMC) with allogeneic Sa cells (an Epstein-Barr virus [EBV]-transformed B-cell line). The CTL did not proliferate in response to UV-B-irradiated Sa cells unless exogenous interleukin-2 (IL-2) was present, although they could kill the UV-B-irradiated Sa cells. The results indicate that UV-B-irradiated Sa cells do not provide sufficient signals for the proliferation of the CTL while they can be recognized by CTL and induce high-affinity IL-2 receptor (IL-2R) expression on them. The alloreactive CTL could be rendered anergic by previous exposure to UV-B-irradiated Sa cells. The alloreactive CTL previously stimulated with UV-B-irradiated Sa cells failed to proliferate in response to nontreated Sa cells. Proliferation of the anergic CTL could not be restored by Sa cells and exogenous IL-2 but by the combination of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore (A23187). The anergic CTL showed a considerably low cytotoxic activity against Sa target cells. The expression of TCR on the anergic CTL was downregulated while expression of high-affinity IL- 2R was upregulated. Their CD28 and CD8 expression were unchanged. In addition, the proliferative response and cytotoxicity of the anergic CTL to Sa cells could be restored after the cells had been rested for 7 days to allow reexpression of TCR. These results suggest that downregulation of T-cell receptor (TCR) and impairment in the post-IL- 2/IL-2R signaling pathway are relevant to the clonal anergy induced in the alloreactive CTL by stimulation of UV-B-irradiated Sa cells.

scholarly journals Neospora caninum-Infected Cattle Develop Parasite-Specific CD4+ Cytotoxic T Lymphocytes

2003 ◽  
Vol 71 (6) ◽  
pp. 3272-3279 ◽  
Author(s):  
Lauren M. Staska ◽  
Travis C. McGuire ◽  
Christopher J. Davies ◽  
Harris A. Lewin ◽  
Timothy V. Baszler
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Neospora Caninum ◽  
Target Cells ◽  
Infected Cattle ◽  
Peripheral Blood Mononuclear ◽  
Histocompatibility Complex ◽  
Immunization Strategies

ABSTRACT Cattle infected with Neospora caninum readily experience transplacental parasite transmission, presumably after maternal parasitemia, leading to abortion or birth of congenitally infected calves. Cytotoxic T lymphocytes (CTL) are important mediators of protective immunity against Toxoplasma gondii, an intracellular apicomplexan protozoan closely related to N. caninum. In this study, N. caninum-specific CTL expanded from peripheral blood mononuclear cells of two major histocompatibility complex-mismatched, experimentally infected cattle were identified by using a 51Cr release cytotoxicity assay. Enrichment and blocking of CD4+- and CD8+-T-lymphocyte effector subsets indicated that CD4+ CTL killed N. caninum-infected, autologous target cells and that killing was mediated through a perforin/granzyme pathway. Detection and characterization of CTL responses to N. caninum in the natural, outbred, bovine host will facilitate identification of immunogens and design of immunization strategies to induce parasite-specific CTL against transplacental N. caninum transmission in cattle.

The kinase insert domain-containing receptor is an angiogenesis-associated antigen recognized by human cytotoxic T lymphocytes

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1476-1483 ◽  
Author(s):  
Yuansheng Sun ◽  
Stefan Stevanović ◽  
Mingxia Song ◽  
Astrid Schwantes ◽  
C. James Kirkpatrick ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Antigenic Property ◽  
Cellular Immunotherapy ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Specific Ctls ◽  
Class 1

Antigen-specific cancer immunotherapy directed toward tumor-nourishing angiogenic blood vessels holds the promise of high efficacy, low toxicity, and ease of application. To evaluate whether the human angiogenic kinase insert domain-containing receptor (KDR) can serve as a target for cellular immunotherapy, 19 peptide sequences with HLA-A*0201 motifs were selected by computer-based algorithms. Five peptides (KDR82-90, KDR288-297, KDR766-774, KDR1093-1101, KDR1035-1044) stimulated specific cytotoxic T lymphocytes (CTLs) from peripheral-blood mononuclear cells (PBMCs) of 3 HLA-A*0201 donors. The decapeptide KDR288-297 was efficient in sensitizing target cells for recognition by a CTL clone at a concentration of 10 nM. More important, KDR288-297 - specific CTLs lysed target cells transfected with HLA-A2/KDR cDNAs and a range of HLA-matched KDR+ angiogenic endothelial cells (aECs) and also recognized CD34+ endothelial progenitor cells. The specificity of CTLs was further confirmed by tetramer assay and cold-target inhibition assay. In addition, ex vivo exposure of aECs to the inflammatory cytokines enhanced CTL reactivity, which is in keeping with up-regulated KDR and HLA class 1 expression. In Matrigel assays, recognition of aECs by specific CTLs triggered an antivascular effect. These findings provide the first proof of the antigenic property of KDR protein and may be useful for devising new immunotherapeutic approaches to human cancers.

Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 1011-1019 ◽  
Author(s):  
Ann M. Leen ◽  
Uluhan Sili ◽  
Barbara Savoldo ◽  
Alan M. Jewell ◽  
Pedro A. Piedra ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Target Cells ◽  
Cell Transplant ◽  
Peripheral Blood Mononuclear ◽  
Hematopoietic Stem ◽  
Considerable Morbidity

AbstractAdenovirus (Ad) infections are responsible for considerable morbidity and mortality, particularly in pediatric hematopoietic stem cell transplant (HSCT) recipients. To date there is no therapy. The present study was motivated by the potential for using adoptive immunotherapy as either prophylaxis or treatment for Ad infections and associated diseases. The authors have developed a protocol to reactivate Ad-specific memory T cells from peripheral blood mononuclear cells (PBMCs) using a clinical-grade adenoviral vector. Such lines contain a specific CD4 and CD8 T-cell component and are capable of recognizing and lysing target cells infected with wild-type Ad serotypes from different Ad groups. Furthermore, the frequency of Ad-specific precursors can be determined in PBMCs ex vivo and used as a means to assess changes in Ad-specific T-cell memory responses after infusion. This is the first report of a simple and reproducible method to activate and expand Ad-specific cytotoxic T lymphocytes (CTLs), which should be protective against the range of different Ad subtypes that affect transplant recipients. (Blood. 2004;103:1011-1019)

scholarly journals Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

2012 ◽  
Vol 2 (4) ◽  
pp. 72 ◽  
Author(s):  
Diana Bayer ◽  
Jonathon Jansen ◽  
Lisa A. Beltz
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Peripheral Blood Mononuclear ◽  
Normal Cells

Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl)-diphenyltetrazolium bromide) assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes. Conclusions: The three tea extracts studied altered leukemic T lymphocyte functions, decreasing cell viability, growth, and production of a major cell growth factor and the H2O2 generated by solutions of extracts may be partially responsible. Normal cells were affected to a far lesser degree by tea extracts and are also more resistant to killing by H2O2 than leukemic cells. This study has implications for using tea extracts for chemotherapeutic and immunomodulatory purposes.Key Words: Tea extracts, interleukin-2, hydrogen peroxide, leukemia, T lymphocytes

scholarly journals Detection of major histocompatibility complex class I-restricted, HIV- specific cytotoxic T lymphocytes in the blood of infected hemophiliacs

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1909-1914 ◽  
Author(s):  
RA Koup ◽  
JL Sullivan ◽  
PH Levine ◽  
D Brettler ◽  
A Mahr ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Class I ◽  
Gene Products ◽  
Major Histocompatibility ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Abstract Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.

scholarly journals A Gene Encoding Antigenic Peptides of Human Squamous Cell Carcinoma Recognized by Cytotoxic T Lymphocytes

1998 ◽  
Vol 187 (3) ◽  
pp. 277-288 ◽  
Author(s):  
Shigeki Shichijo ◽  
Masanobu Nakao ◽  
Yasuhisa Imai ◽  
Hideo Takasu ◽  
Mayumi Kawamoto ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Squamous Cell ◽  
Mononuclear Cells ◽  
Tumor Antigens ◽  
Autologous Tumor ◽  
Antigenic Peptides ◽  
Proliferating Cells ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear

Except for melanomas, tumor antigens recognized by cytotoxic T lymphocytes (CTLs) are yet unidentified. We have identified a gene encoding antigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)- A2601–restricted CTLs. This gene showed no similarity to known sequences, and encoded two (125- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leucine zipper motif was expressed in the nucleus of the majority of proliferating cells tested, including normal and malignant cells. The 43-kD protein was expressed in the cytosol of most SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein and this nonapeptide (KGSGKMKTE) may be useful for the specific immunotherapy of HLA-A2601+ epithelial cancer patients.

scholarly journals Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1044-1049 ◽  
Author(s):  
K Oshimi ◽  
T Seto ◽  
Y Oshimi ◽  
M Masuda ◽  
K Okumura ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr- labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.

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