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41.
T-cell activation requires the interaction of the T-cell receptor with a cognate major histocompatibility complex (MHC)-peptide complex. Initiated by antigen engagement, the adaptive immune response is orchestrated by a complex balance between stimulatory and inhibitory signals that are predominantly controlled by members of the B7 family. Here, we review the current knowledge on B7 family members concerning their constitutive and regulated expression, modulation of the immune response and their role in the evasion of host immune surveillance. We also discuss recent therapeutic strategies that aim to improve immune-cell recognition of tumors and induce tolerance to autoreactive immune responses in normal tissues by manipulating B7 functions. 相似文献
42.
43.
Verheyden S Ferrone S Mulder A Claas FH Schots R De Moerloose B Benoit Y Demanet C 《Cancer immunology, immunotherapy : CII》2009,58(6):855-865
Transplantation of acute myeloid leukemia (AML) patients with grafts from related haploidentical donors has been shown to
result in a potent graft-versus-leukemia effect. This effect is mediated by NK cells because of the lack of activation of
inhibitory killer cell immunoglobulin-like receptors (KIRs) which recognize HLA-Bw4 and HLA-C alleles. However, conflicting
results have been reported about the impact of KIR ligand mismatching on the outcome of unrelated HLA-mismatched hematopoietic
stem cells transplants (HSCT) to leukemic patients. The interpretation of these conflicting results is hampered by the scant
information about the level of expression of HLA class I alleles on leukemic cells, although this variable may affect the
activation of inhibitory KIRs. Therefore in the present study, utilizing a large panel of human monoclonal antibodies we have
measured the level of expression of HLA-A, -B and -C alleles on 20 B-chronic lymphoid leukemic (B-CLL) cell preparations,
on 16 B-acute lymphoid leukemic (B-ALL) cell preparations and on 19 AML cell preparations. Comparison of the level of HLA
class I antigen expression on leukemic cells and autologous normal T cells identified selective downregulation of HLA-A and
HLA-B alleles on 15 and 14 of the 20 B-CLL, on 2 and 5 of the 16 B-ALL and on 7 and 11 of the 19 AML patients tested, respectively.
Most interestingly HLA-C alleles were markedly downregulated on all three types of leukemic cells; the downregulation was
most pronounced on AML cells. The potential functional relevance of these abnormalities is suggested by the dose-dependent
enhancement of NK cell activation caused by coating the HLA-HLA-Bw4 epitope with monoclonal antibodies on leukemic cells which
express NK cell activating ligands. Our results suggest that besides the HLA and KIR genotype, expression levels of KIR ligands
on leukemic cells should be included among the criteria used to select the donor-recipient combinations for HSCT. 相似文献
44.
Chin-Hsuan Hsieh Ya-Jan Hsu Chien-Chung Chang Hsin-Chun Liu Kun-Lung Chuang Cheng-Keng Chuang See-Tong Pang Kenichiro Hasumi Soldano Ferrone Shuen-Kuei Liao 《Cancer immunology, immunotherapy : CII》2009,58(3):395-408
In renal cell carcinoma (RCC), HLA class I downregulation has been found in about 40% of the lesions examined. Since only
scanty information is available about the molecular basis of these defects, we have investigated the mechanism(s) underlying
HLA class I antigen downregulation or loss in six RCC cell lines. Five of them express HLA class I antigens although at various
levels; on the other hand, HLA class I antigens are not detectable on the remaining cell line, the RCC52 cell line, belonging
to a sarcomatoid subtype, even following incubation with IFN-γ. β2-microglobulin (β2
m) was not detected in RCC52 cells. Surprisingly, RCC52 cells harbor two mutations in the β
2
m genes in exon 1: a single G deletion (delG) in codon 6, which introduces a premature stop at codon 7, and a CT dinucleotide
deletion (delCT), which leads to a premature stop at codon 55. Analysis of eight clonal sublines isolated from the RCC52 cell
line showed that the two β
2
m gene mutations are carried separately by RCC52 cell subpopulations. The delG/delCT double mutations were detected in two
sublines with a fibroblast-like morphology, while the delCT mutation was detected in the remaining six sublines with an epithelial
cell morphology. Furthermore, loss of heterozygosity (LOH) of the β
2
m gene at STR D15S-209 was found only in the epithelioid subpopulation, indicating loss of one copy of chromosome 15. Immunostaining
results of the tumor lesion from which the cell line RCC52 was originated were consistent with the phenotyping/molecular findings
of the cultured cells. This is the first example of the coexistence of distinct β
2
m defects in two different tumor subpopulations of a RCC, where loss of one copy of chromosome 15 occurs in one of the subpopulations
with total HLA class I antigen loss.
Chin-Hsuan Hsieh, Ya-Jan Hsu and Cheng-Keng Chuang contributed equally to the work. 相似文献
45.
Maurizio Cutolo Stefano Soldano Paola Montagna Alberto Sulli Bruno Seriolo Barbara Villaggio Pierfranco Triolo Paolo Clerico Lamberto Felli Renata Brizzolara 《Arthritis research & therapy》2009,11(6):R176-10
Introduction
Co-stimulatory signal B7(CD80/CD86):CD28 is needed in order to activate T cells in immune response. Cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4-Ig) binding to the B7 molecules on antigen-presenting cells downregulates this activation and represents a recent biological treatment in rheumatoid arthritis (RA). Objectives of the study were to investigate the presence of the B7.2 (CD86) molecule and its masking by CTLA4-Ig on cultures of both RA synovial macrophages (RA SM), and of macrophages differentiated from THP-1 cells (M). In addition, the anti-inflammatory effects of CTLA4-Ig on co-cultures of RA SM and M with activated T cells were tested. 相似文献46.
47.
Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2''''-deoxycytidine 总被引:2,自引:0,他引:2
~~Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2'-deoxycytidine@Chien Chung CHANG$Department of Immunology,Roswell Park Cancer Institute,Buffalo.NY 14263,USA
@Soldano FERRONE$Department of Immunology,R… 相似文献
48.
49.
Various mutants have been obtained of B. brongniartii, a hyphomycete pathogenic for insects. Both one pigment less and two blastospore negative mutants retained their initial virulence. Thus neither the characteristic parasitic blastospore morphology nor the synthesis of the pigment appeared to be required for pathogenesis. Analysis of avirulent mutants indicated that chitinolytic activity may be essential for fungal penetration of the cuticle. 相似文献