Search results for "HLA Antigens"
showing 10 items of 96 documents
Altered expression of nonclassical HLA class Ib antigens in human renal cell carcinoma and its association with impaired immune response
2003
Abstract An optimal antitumoral immune response requires the activation of both CD8 + and CD4 + T lymphocytes by the peptide antigen presentation via the human leukocyte antigen (HLA) class I and class II molecules, respectively. Downregulation or loss of HLA molecules has been found in human renal cell carcinoma (RCC) and provides a strategy of these tumors to evade T-cell mediated immunosurveillance. In addition, a tumor-specific upregulation of HLA-G has been recently described in RCC, which also leads to an impaired immune response. We here summarize the frequency of the constitutive and/or interferon-γ (IFN-γ) inducible expression of nonclassical HLA class Ib antigens in RCC cell lines…
Liver-infiltrating and circulating CD4+ T cells in chronic hepatitis C: immunodominant epitopes, HLA-restriction and functional significance.
2008
The aim was to assess the specificity and functional significance of liver-infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a proliferative T cell response to at least one of 16 synthetic peptides covering highly conserved regions of the core, envelope (El) and non-structural regions (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively recognized by the proliferating blood mononuclear cells from 46 patients with chronic hepatitis C virus infection (79.3%). Fine specificity and HLA-restri…
Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines.
2006
AbstractIn HLA-incompatible hematopoietic stem cell transplantation, alloreactive donor T cells recognizing recipient mismatch HLA cause severe graft-versus-host disease (GVHD). Strategies allowing the selective depletion of alloreactive T cells as well as the enhancement of graft-versus-malignancy immunity would be beneficial. We generated donor CD8 T-cell lines in vitro using allogeneic recipient cells mismatched at a single HLA class I allele or haplotype as stimulators. Recipient cells were obtained from acute myeloid leukemias, renal-cell carcinomas, and CD40L-induced B lymphoblasts. Resulting alloreactive T cells were activated by incubating day 21 T-cell cultures with HLA-mismatch tr…
Alloreactive and leukemia-reactive T cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with me…
2011
Background HLA mismatch antigens are major targets of alloreactive T cells in HLA-incompatible stem-cell transplantation, which can trigger severe graft- versus -host disease and reduce survival in transplant recipients. Our objective was to identify T-cell subsets with reduced in vitro reactivity to allogeneic HLA antigens. Design and Methods We sorted CD4 and CD8 T-cell subsets from peripheral blood by flow cytometry according to their expression of naive and memory markers CD45RA, CD45RO, CD62L, and CCR7. Subsets were defined by a single marker to facilitate future establishment of a clinical-grade procedure for reducing alloreactive T-cell precursors and graft- versus -host disease. T c…
B7-1 and B7-2 act differentially in the induction of a T cell response: their impact for a HLA-matched and HLA-mismatched anti-tumor immunotherapy.
2005
The efficacy of T cell-based immunotherapy is primarily due to efficient cellular activation that requires the engagement of 2 separate signals, i.e., via the T cell receptor complex and via co-stimulatory molecules the prototype of which is CD28. In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are thought to play nearly identical roles in T cell activation. We monitored the T cell response upon co-culture with HLA Class I-matched and mismatched renal carcinoma cells, respectively, that express different levels of B7-1 and B7-2, respectively. In a HLA Class I-mismatched co-culture, T cell proliferation, IFN-γ and GM-CSF secretion equally depend on the levels of B7-1 and…
Advances in haploidentical stem cell transplantation for hematologic malignancies
2016
One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We als…
Presence on a human melanoma of multiple antigens recognized by autologous CTL.
1989
We derived from blood lymphocytes of a melanoma patient a large number of cytolytic T-cell clones directed against a cell line of the autologous tumor. Three distinct groups of antigens were recognized by these CTL on the autologous melanoma cells: group A consisted of stable antigens present on all sublines, whereas antigens B and C appeared unstable and were expressed by distinct sublines. In vitro immunoselections with various anti-A CTL clones were applied to the melanoma cells and variants resistant to 3 different CTL clones were obtained. These variants remained sensitive to other anti-A CTL clones, indicating that group A comprises at least 4 different antigens (D, E, F and A'). From…
Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation.
2005
In humans as in other animal species, CD8+ cytotoxic T lymphocytes (CTLs) play an important if not the major role in controlling virus-infected and malignant cell growth. The interactions between CD8+ T cells and target cells are mediated by human leukocyte antigen (HLA) class I antigens loaded with viral and tumor antigen-derived peptides along with costimulatory receptor/ligand stimuli. Thus, to escape from CD8+ T-cell recognition and destruction, viruses and tumor cells have developed strategies to inhibit the expression and/or function of HLA class I antigens. In contrast, cells with downregulated MHC class I surface expression can be recognized by NK cells, although NK cell-mediated ly…
Low frequency of HLA haplotype loss associated with loss of heterozygocity in chromosome region 6p21 in clear renal cell carcinomas.
2004
HLA class I loss or downregulation is a widespread mechanism used by tumor cells to avoid tumor recognition by cytotoxic T lymphocytes favoring tumor immune escape. Multiple molecular mechanisms are responsible for these altered HLA class I tumor phenotypes. It has been described in different epithelial tumors that loss of heterozygosity (LOH) at chromosome region 6p21.3 is a frequent mechanism that leads to HLA haplotype loss, ranging between 40 and 50%, depending on the tumor entity analyzed. Here we have tested the frequency of LOH at 6p21 chromosome region in Renal Cell Carcinomas (RCC) of the clear cell and chromophobe subtype. A low frequency of HLA haplotype loss (6.6%) was found in …
Effects of interferon gamma on the proliferation and modulation of cell-surface structures of human ovarian carcinoma cell lines.
1993
Platinum-containing regimens are very effective in the primary treatment of ovarian cancer. However, upon subsequent treatment most tumors develop multidrug resistance. The clinical application of biological response modifiers like interferon gamma (IFN gamma) in advanced ovarian cancer is therefore of increasing interest. Permanent ovarian cancer cell lines are suitable for investigating the mode of action and the potential clinical effectiveness of such response modifiers. IFN gamma is known to modulate many cellular functions. In this study it was compared for its antiproliferative and antigen-modulatory activity on the expression of tumor-associated (CA-125, HMFG, CEA) and major histoco…