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 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 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.

SART1 Gene Encoding Squamous Cell Carcinoma Antigen Recognized by Cytotoxic T Lymphocytes

Cell Therapy ◽  
2000 ◽  
pp. 15-28
Author(s):  
Kyogo Itoh ◽  
Shigeki Shichijo ◽  
Yoshiko Inoue ◽  
Akihiro Hayashi ◽  
Uhi Toh ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Lymphocytes ◽  
Cell Carcinoma ◽  
Cytotoxic T Lymphocytes ◽  
Squamous Cell ◽  
Squamous Cell Carcinoma Antigen ◽  
Gene Encoding

Ex vivo induction of multiple myeloma–specific cytotoxic T lymphocytes

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1435-1442 ◽  
Author(s):  
Toshiaki Hayashi ◽  
Teru Hideshima ◽  
Masaharu Akiyama ◽  
Noopur Raje ◽  
Paul Richardson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Stimulation Index ◽  
T Cell Proliferation ◽  
Autologous Tumor

Abstract Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by immunosuppression. In this study, we identified factors in patients' bone marrow (BM) sera inhibiting autologous anti-MM immunity and developed an ex vivo strategy for inducing MM-specific cytotoxic T lymphocytes (CTLs). We found that sera from BM of MM patients inhibited induction of dendritic cells (DCs), evidenced by both phenotype and only weak stimulation of T-cell proliferation. Anti–vascular endothelial growth factor (anti-VEGF) and/or anti–interleukin 6 (anti–IL-6) antibodies neutralized this inhibitory effect, confirming that VEGF and IL-6, at least in part, mediate immunosuppression in MM patients. To induce MM-specific CTLs ex vivo, immature DCs were generated by culture of adherent mononuclear cells in medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 for 5 days and then cocultured with apoptotic MM bodies in the presence of tumor necrosis factor α (TNF-α) for 3 days to induce their maturation. Autologous BM or peripheral blood mononuclear cells were stimulated weekly with these DCs, and cytotoxicity was examined against the MM cells used to pulse DCs. DCs cultured with apoptotic bodies stimulated significantly greater T-cell proliferation (stimulation index [SI] = 23.2 at a T-DC ratio of 360:1) than T cells stimulated by MM cells only (SI = 5.6), DCs only (SI = 9.3), or MM lysate–pulsed DCs (SI = 13.5). These CTLs from MM patients demonstrated specific cytotoxicity (24.7% at the effector-target [E/T] ratio of 40:1) against autologous primary MM cells. These studies therefore show that CTLs from MM patients can recognize and lyse autologous tumor cells and provide the framework for novel immunotherapy to improve patient outcome in MM.

scholarly journals Detection of JC Virus-Specific Cytotoxic T Lymphocytes in Healthy Individuals

2004 ◽  
Vol 78 (18) ◽  
pp. 10206-10210 ◽  
Author(s):  
R. A. Du Pasquier ◽  
J. E. Schmitz ◽  
J. Jean-Jacques ◽  
Y. Zheng ◽  
J. Gordon ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Jc Virus ◽  
T Cell Response ◽  
Healthy Individuals ◽  
Peripheral Blood Mononuclear ◽  
Specific Ctls ◽  
The Central Nervous System

ABSTRACT The polyomavirus JC (JCV) infects 85% of healthy individuals, and its reactivation in a limited number of immunosuppressed people causes progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. We hypothesized that JCV-specific cytotoxic T lymphocytes (CTLs) might control JCV replication in healthy individuals, blocking the evolution of PML. Using 51Cr release and tetramer staining assays, we show that 8 of 11 HLA-A*0201+ healthy subjects (73%) harbor detectable JCV-specific CD8+ CTLs that recognize one or two epitopes of JCV VP1 protein, the HLA-A*0201-restricted VP1p36 and VP1p100 epitopes. We determined that the frequency of JCV VP1 epitope-specific CTLs varied from less than 1/100,000 to 1/2,494 peripheral blood mononuclear cells. More individuals had JCV VP1-specific than cytomegalovirus-specific CTLs (8 of 11 subjects [73%] versus 2 of 10 subjects [20%], respectively). These results show that a CD8+-T-cell response against JCV is commonly found in immunocompetent people and suggest that these cells might protect against the development of PML.

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

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.

Efficient induction of specific cytotoxic T lymphocytes against gastric adenocarcinoma by a survivin peptide

2012 ◽  
Vol 90 (6) ◽  
pp. 701-708 ◽  
Author(s):  
Yi Gang ◽  
Xiaoyin Zhang ◽  
Yuanlong He ◽  
Jianyong Zheng ◽  
Kaichun Wu ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Gastric Adenocarcinoma ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Epitope Peptide ◽  
Peripheral Blood Mononuclear ◽  
Simple Method ◽  
Healthy Donors ◽  
Efficient Induction

Survivin has been demonstrated to be an excellent target for immunotherapy in several types of cancer, but little is known of the efficacy of survivin with gastric adenocarcinoma. In this study, a simple method was performed, and relatively high efficacy was shown upon inducing survivin-derived peptide-specific cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells of healthy donors. The induced CTLs exhibited specific lysisagainstHLA-A2 matched tumor cells in vitro, and similar results were demonstrated in primary cell cultures isolated from patients with gastric adenocarcinoma. Up to 30% of randomly selected patients could potentially benefit from immunotherapy targeting survivin. These results suggested that this survivin epitope peptide could be a promising vaccine candidate for immunotherapy for patients with gastric adenocarcinoma.

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