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1.
Immunobiology ; 203(5): 725-42, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11563673

ABSTRACT

We have established a novel monoclonal antibody that recognises mouse and rat CD157, and uncovered striking differences in both the level and stage of expression of this antigen in the primary lymphoid organs between these two species. Unlike mouse, the majority of rat thymocytes express CD 157. SHR and WKY rats were the exception, having unusually low levels (similar to those of the mouse) of these cells. However, in both species, a subset of CD3- CD4- CD8- thymocytes exhibited high levels of CD157. Surprisingly, these CD157high cells temporarily upregulated MHC class I molecules in both species. Furthermore, a third of CD157high rat thymocytes were CD45RC+, a marker found on immature thymocytes with regenerative capacity. Examination of the bone marrow lymphoid population shows that the expression of rat CD157 is largely observed at the CD45R+ IgM- pre-B-II cell stage, and unlike mouse, extension of expression into the IgM+ immature B cell stage was marginal. Similar to CD157high immature thymocytes, these immature B cells also expressed high levels of MHC class I. With the exception of the LEC, SHR and WKY rat strains, which have three- to four-fold less CD157+ bone marrow myeloid cells, percentages of these cells are similar between these two species. Thus, marked differences in the level and stage(s) of CD157 expression on lymphoid cells in mouse and rat indicate that CD157 may not, as previously thought, have a direct role in T or B cell differentiation.


Subject(s)
ADP-ribosyl Cyclase , Antigens, CD , Biomarkers/analysis , Lymphocytes/immunology , Membrane Glycoproteins/pharmacology , Mice, Inbred Strains/immunology , Rats, Inbred Strains/immunology , Animals , Antibodies, Monoclonal , Antibody Specificity , Bone Marrow Cells/immunology , CHO Cells , Cell Differentiation , Cells, Cultured , Cricetinae , GPI-Linked Proteins , Lymphocyte Subsets/immunology , Mice , Rats , Species Specificity , Thymus Gland/immunology , Tissue Distribution
5.
Cancer Lett ; 108(2): 281-90, 1996 Nov 29.
Article in English | MEDLINE | ID: mdl-8973606

ABSTRACT

To investigate the relationship between tumor angiogenesis and the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/dThdPase) and between patients' survival and the expression of PD-ECGF/ dThdPase in human gastric carcinoma tissues, we performed immunohistochemical studies with anti-PD-ECGF/dThdPase and anti-CD34 monoclonal antibodies. Out of 154 gastric carcinoma tissue samples, 61 (40%) were evaluated as PD-ECGF/ dThdPase-positive. The expression of PD-ECGF/dThdPase was significantly associated with the intratumoral microvessel counts (P < 0.0001) and the incidence of hematogenous metastasis (P < 0.05). Intratumoral vessel counts were significantly correlated with overall survival of 154 patients (P < 0.000001). Cox proportional hazards model showed that tumor vasculature was an independent and strong prognostic variable. However, the prevalence of the expression of PD-ECGF did not associate the overall survival. We suggest that expression of PD-ECGF/dThdPase plays a role in the promotion of angiogenesis in human gastric carcinomas, without any definite influence on patient's survival.


Subject(s)
Adenocarcinoma/enzymology , Neovascularization, Pathologic/physiopathology , Platelet-Derived Growth Factor/metabolism , Stomach Neoplasms/enzymology , Thymidine Phosphorylase/metabolism , Adenocarcinoma/blood supply , Aged , Blotting, Western , Female , Humans , Male , Middle Aged , Stomach Neoplasms/blood supply , Survival Analysis
6.
J Immunol ; 155(8): 4046-51, 1995 Oct 15.
Article in English | MEDLINE | ID: mdl-7561115

ABSTRACT

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis. While products of the MHC are known to control the development of EAE, it is clear that non-MHC products also influence susceptibility. The chromosomal locations of these were investigated in selective crosses between MHC class II-compatible, EAE-susceptible Biozzi ABH, and low responder nonobese diabetic (NOD) mice. The disease was dominant and highly influenced by gender in the backcross one (BC1) generation. Female mice were significantly more susceptible than male mice. Segregation of disease frequency of female animals in this cross suggested that EAE was controlled by a major locus. Although microsatellite-based exclusion mapping indicated that a number of regions on chromosomes 5, 6, 7, 8, 9, 10, 11, 12, 13, and 18 showed evidence of linkage (p < 0.05) compared with expected random distributions of alleles, disease susceptibility was most strongly linked (p < 0.001) to chromosome 7. However, by selectively analyzing animals that were either severely affected or almost normal, additional susceptibility loci were mapped on chromosomes 18 and 11 that were linked (p < 0.001) to resistance and the development of severe disease, respectively. The data indicate a major locus on chromosome 7, affecting initiation and severity of EAE that is probably modified by several other unlinked loci. These localizations may provide candidate loci for the analysis of human autoimmune-demyelinating disease.


Subject(s)
Chromosome Mapping , Encephalomyelitis, Autoimmune, Experimental/genetics , Animals , Chromosome Mapping/methods , Crosses, Genetic , DNA, Satellite/analysis , Female , Genetic Predisposition to Disease , Male , Mice , Mice, Inbred NOD , Mice, Inbred Strains
8.
Immunol Rev ; 131: 131-68, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8387455

ABSTRACT

In mice, V beta-specific negative selection is mediated by a number of superantigens encoded by various mouse mammary tumor viruses. We have identified Mtv-3, Mtv-27, Mtv-44, Mtv-8, Mtv-9, Mtv-11, and MMTV(D2.GD), and have confirmed Mtv-1. Although specificities of superantigens correlate well with sequences of their carboxy terminal regions, Mtv-44 appears to be an exception: the product is specific for V beta 3, V beta 6, V beta 8.1, and V beta 9. It remains to be determined whether Mtv-44 produces one or two different superantigens to exhibit this specificity. V beta 5+ T-cell deletion is induced by two groups of superantigens: V beta 3-specific superantigens encoded by Mtv-1, Mtv-3, Mtv-6, Mtv-13, Mtv-27, and Mtv-44, and V beta 11-specific superantigens encoded by Mtv-8, Mtv-9, and Mtv-11. Furthermore, these V beta 3-specific superantigens are also specific for V beta 17a(cz). In contrast, V beta-specific positive selection and V alpha-specific positive and negative selection do not seem to involve non-H-2 (super)antigens, although their involvement can not be excluded. In the near future, superantigens, powerful modulators of T-cell functions, will be exploited for clinical applications.


Subject(s)
Antigens, Viral , Receptors, Antigen, T-Cell, alpha-beta , Amino Acid Sequence , Animals , Antibodies, Viral , Antigens, Viral/genetics , Gene Deletion , Mammary Tumor Virus, Mouse/genetics , Mammary Tumor Virus, Mouse/immunology , Mice , Molecular Sequence Data , Receptors, Antigen, T-Cell, alpha-beta/genetics , T-Lymphocytes/immunology
10.
Int Rev Immunol ; 8(4): 289-309, 1992.
Article in English | MEDLINE | ID: mdl-1318935

ABSTRACT

It has recently become clear that the minor lymphocyte stimulatory antigens (Mls) and other endogenous ligands which lead to the partial or total deletion of T cells bearing particular V beta segments are encoded by mouse mammary tumor virus (MMTV). We review here the genetic analyses of multiple V beta 11 and V beta 3 deletion ligands and demonstrate the involvement of MMTV in all examples. Several features of Mls and the V beta 11/V beta 3 deleting ligands identify them as members of the superantigen family. Bacterial superantigens are known to bind both MHC class II and the TCR in regions distinct from conventional peptide antigens. Within the MMTV genome, the 3' LTR has been identified as encoding superantigen function. We present data demonstrating that in vitro translation identifies the major product of the open reading frame (ORF) within the 3' LTR as a type II integral membrane glycoprotein. It is proposed that the type II membrane glycoprotein interacts with MHC and TCR in a manner analogous to the bacterial superantigens and distinct from conventional peptide antigen. Several unanswered questions regarding superantigen action remain; what determines total or partial deletion? How is Mls transferred between cells? These questions are addressed in the discussion.


Subject(s)
Receptors, Antigen, T-Cell, alpha-beta/genetics , T-Lymphocytes/immunology , Animals , Chromosome Deletion , Ligands , Major Histocompatibility Complex/genetics , Mammary Tumor Virus, Mouse/genetics , Membrane Glycoproteins/genetics , Minor Lymphocyte Stimulatory Antigens/genetics , Open Reading Frames , Signal Transduction
11.
Immunogenetics ; 36(3): 189-94, 1992.
Article in English | MEDLINE | ID: mdl-1319398

ABSTRACT

Genes encoding endogenous superantigens causing Tcrb-V3+ T-cell deletion co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-3, Mtv-6, and Mtv-13. In addition Mtv-1 has been implicated in deletion of these T cells. We have examined levels of Tcrb-V3+ T cells and Mtv integrations in the following offspring and their parental strains, [(CBA-T6 x NZW)F1 x CBA], [(CBA x C3H/He)F1 x CBA], and [(B10.S (9R) x NOD]F1 mice. We show that a new Mtv (Mtv-44) from NZW mice and Mtv-1 from C3H/He mice cosegregate with genes encoding ligands for partial deletion of Tcrb-V3+ T cells and that some NOD mice have an additional Mtv (Mtv-45) which is closely linked to Mtv-3.


Subject(s)
Antigens, Viral/genetics , Gene Rearrangement, beta-Chain T-Cell Antigen Receptor , Mammary Tumor Virus, Mouse/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , T-Lymphocytes/physiology , Animals , Blotting, Southern , Chromosome Deletion , Ligands , Mammary Tumor Virus, Mouse/immunology , Mice , Mice, Inbred Strains , Proviruses/genetics
12.
Immunogenetics ; 36(5): 302-5, 1992.
Article in English | MEDLINE | ID: mdl-1322864

ABSTRACT

Genes encoding superantigens which delete Tcrb-V3+ T cells co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-1, Mtv-3, Mtv-6, Mtv-13, and Mtv-44. We have examined percentages of Tcrb-V3+ T cells and Mtv integrations in [(B10 x NZB)F1 x B10.BR] mice, and show that Mtv-27 as well as Mtv-3 from NZB mice co-segregate with genes encoding deletion ligands for Tcrb-V3+ T cells without recombination.


Subject(s)
Mammary Tumor Virus, Mouse/genetics , Proviruses/genetics , Receptors, Antigen, T-Cell, alpha-beta/analysis , T-Lymphocytes/immunology , Animals , Blotting, Southern , Genome, Viral , Lymphocyte Depletion , Mice , Mice, Inbred C57BL , Mice, Inbred NZB
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