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Biomedical subjects

H Festenstein

Publications and source records attributed to H Festenstein.

249 records · Page 14Linked to original sources

Immunogenetic studies of multiple sclerosis patients in Caithness County, Scotland.

The present report indicates that there is an increased frequency of HLA-B7 in multiple sclerosis patients compared to unrelated controls and unaffected siblings. HLA-A3 was not significantly increased. The increased frequency of certain HLA antigens was not reflected in increased titres of serum measles antibodies in this group. In contrast to our previous studies, there were only minimal differences in the cellular response to measles antigen in multiple sclerosis patients as compared to siblings and unrelated controls.

Adult↗

HLA class I and class II antigen associations in acute leukaemias.

HLA-A,B,C and DR antigen frequencies were determined in a group of 188 patients suffering from acute myeloid (AML) and acute lymphoid leukaemia (ALL). These antigen frequencies were compared with those obtained on a panel of normal individuals (n = 109) of the same ethnic origin. The significance of the differences in the antigen distribution and the strength of the associations between particular HLA antigens and the disease were then calculated. The results obtained show a decreased frequency of HLA-Aw19 in the overall group of patients and the group of patients with ALL. In addition, the antigen frequency of the HLA-B18 and DR5(DRw11) antigens was also decreased in the overall group of patients and in those patients with AML but not in the patients with ALL. The results suggest that the antigen Aw19 may confer some degree of resistance to the development of ALL and that the HLA-B18 and/or DR5 antigens may be resistance factors for the development of AML.

Adolescent↗

Aberrant H-2-like allospecificities on K36.16 thymoma. Studies by radiobinding and immunoprecipitation with anti-H-2 monoclonal antibodies.

The K36.16 thymoma expresses an H-2Dd-like allospecificity as detected by the 34-5-8 monoclonal antibody directed against H-2Dd using immunoprecipitation techniques. This monoclonal antibody gives a negative result by radio-immune assay but other anti-Dd antibodies react positively with this tumour. These results confirm and extend previous observations and are attributed to probable gene-conversion events possibly involving a donor gene from the Qa/Tla region, the products of which cross-react with Dd.

Animals↗

Structural variations in the H-2 genes of AKR lymphomas.

K36.16 is an AKR H-2k thymoma which expresses an aberrant H-2Dd-like allospecificity, does not have a detectable amount of the H-2Kk syngeneic antigen and grows very easily in syngeneic mice. By DNA-mediated gene transfer experiments, we were able to obtain transformed clones which do express the H-2Kk molecules and are rejected by AKR mice. Southern hybridization was performed to assess whether any gross changes had occurred in the K36.16 H-2K locus or elsewhere in the MHC, which might explain the lack of H-2K expression and/or the presence of the aberrant H-2Dd-like allospecificity. Specific H-2 class I DNA probes were used to compare the K36.16 genomic DNA with normal AKR thymus DNA after digestion with a variety of restriction enzymes. After hybridization with the pH-2IIa probe a 2.8 kb 'Hind III' fragment was identified in the K36.16 genomic DNA which is absent from AKR DNA. The pH-2IIa probe detects the third, transmembrane and cytoplasmic domains of class I genes. Although these changes are indicative of MHC genome modifications it is not yet possible to link these specific Southern blot pattern variations with the phenotypic changes mentioned above.

Animals↗

Modulation of the expression of HLA class II antigens by gamma interferon and phorbol ester TPA on myeloid leukaemic cell lines.

We investigated the effect of gamma interferon and phorbol ester (TPA), on the expression of HLA class II molecules of myeloid leukaemic cell lines K562, U937, KG-1, HL-60 and ML-2. Gamma interferon induced the expression of HLA-DR but not HLA-DQ on HL-60 and ML-2, increased the expression of HLA-DR and DQ on U937 and induced the expression of HLA-DQ on KG-1. TPA treatment did not affect the expression of HLA class II antigens on U937 and KG-1 and induced the expression of HLA-DR and HLA-DQ on HL-60 and ML-2. TPA treatment did not affect the HLA phenotype of K562 but gamma interferon did induce HLA class I molecules. Thus, gamma interferon cannot only increase the expression of HLA products already expressed on the cells but can also induce the de novo synthesis of these molecules on myeloid leukaemic cell lines.

Cell Line↗

The expression of murine Qa region gene product(s) in L cell transformants.

The cosmid H3.5, containing genes mapping to the murine H-2 Qa region, was used to transfect L cells by the calcium phosphate co-precipitation method. The resultant transfected cells expressed a Qa-like determinant as detected by an immune serum raised against the transfectant cells and Qa specific monoclonal antibodies. Two-dimensional gel analysis revealed the expression of a class I-like heavy chain with a similar molecular mass to the Qa2 antigens of the positive strain B10 and B10.A but with a different isoelectric point. The cosmid H3.5 spans 40 kb of DNA and contains at least one complete Qa region gene which encodes the Qa-like determinant detected in this study.

Animals↗

Abrogation of lethal graft-versus-host reaction directed against non-H-2 antigens: role of Mlsa and K/I region antigens in the induction of unresponsiveness by alloimmunization.

A graft-versus-host reaction (GVHR) directed against DBA/2 non-H-2 antigens alone can be induced by grafting B10.D2 bone marrow and spleen cells intravenously to heavily irradiated, H-2d compatible (DBA/2 X B10.D2)F1 adult mice. Under the experimental conditions used, only 0-10% of recipients survive, but the survival is greatly increased by donor alloimmunization, a few days prior to grafting, against host-specific (DBA/2) non-H-2 antigens and non-specific (foreign) H-2 antigens. The increased survival is mediated by alloimmunization-activated suppressor cells which can decrease the intensity of the immune reaction developed by normal B10.D2 cells both in vivo (GVHR) and in vitro (proliferative response measured in mixed lymphocyte culture, MLC). The present experiments were designed to explore the antigenic requirements for inducing suppression. The results showed that in GVHR the protective effect induced by donor alloimmunization against the specific non-H-2 antigens, which leads to 70-80% survival, is due primarily, if not entirely, to immunization against Mlsa antigens. Results of MLC experiments confirmed this conclusion, showing that immunization against Mlsa antigens is sufficient to account for the suppressive effect induced by the specific immunization. In addition, they indicated that the non-specific protective effect induced by donor alloimmunization against foreign H-2 antigens, which leads to 20-30% survival, is due to immunization against antigens encoded by the K and/or I region(s) of the H-2 complex; immunization against D region encoded antigens alone has no effect.

Animals↗

T cells define new alloantigens controlled by a gene(s) in the M1s region on mouse chromosome 1.

Two different types of T cell clones which recognize Mlsb haplotype gene products were established by using mice congenic at the Mls locus. The antigens defined by these T cells showed differences not only in strain distribution but also in the restriction element for antigen recognition by T cells (i.e. Kd or Dd). The antigens appear to be expressed on various types of lymphocytes.

Alleles↗

Functional studies of H-2k-like epitopes on DTIC treated and untreated L1210 (H-2d) clones.

Following 'in vivo' treatment with 5-(3-3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), murine leukemic cells acquire new antigenic specificities not detectable on parental cells and responsible for the rejection of the tumour by syngeneic hosts. 'In vivo' and 'in vitro' experiments pointed out an immunological cross reactivity between DTIC treated and untreated lines. Furthermore, specific CTLs raised against DTIC treated L1210 tumour cells (H-2d) were cytotoxic for H-2k target cells. The aim of this study is to investigate whether the H-2k cross reactivity displayed by L1210/DTIC is related to the drug treatment rather than due to an antigen already present in the parental line and maintained after treatment. Cloned cells from L1210, obtained by limiting dilution 'in vitro', were recloned 'in vivo' and then treated with DTIC. Syngeneic and allogeneic CTLs raised 'in vitro' against parental and treated clones showed lytic activity against H-2k target cells. Treated and untreated clones were then checked for the presence of H-2k-like determinants using monoclonal antibodies. One of these, HB-53 (IgG2bKkDk) was highly positive with all the clones tested in binding assay using iodinated Fab anti-mouse Ig, fluorescence and FACS analysis. Others displayed a low reactivity against both treated and untreated clones without significant differences. After neuraminidase treatment of two clones (D and D/DTIC), the H-100.5 (anti H-2Kk)-reactive epitope was dramatically exposed on the DTIC tumour cells but not on the parental clones. These data suggest that the H-2k cross reactivity is related to the presence of a TAA that is maintained after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biological significance of beta hCG, HLA and other membrane antigen expression on bladder tumours and their relationship to tumour infiltrating lymphocytes (TIL).

Expression of beta human chorionic gonadotropin (beta hCG) by bladder tumours has been shown to be associated with increased metastases and resistance to treatment with radiotherapy and chemotherapy. Preliminary results from typing frozen tumours using monoclonal antibodies against HLA determinants show reduced or lost expression of one or more antigens in two thirds of patients studied with a trend for more malignant behaviour and inability to generate tumour infiltrating lymphocyte expression using Interleukin-2 in those patients whose tumours demonstrate loss. In this series beta hCG expression was only seen in a subgroup of those demonstrating loss of HLA antigen expression. Studies of beta hCG secreting bladder cancer cell lines showed that it was possible to induce class II HLA antigen expression with gamma Interferon, and that this treatment but not alpha Interferon reduced beta hCG production by the cell line.

Antigens, Surface↗

Protection of newborn mice from graft versus host disease by maternal pre-immunization.

Alloimmunization of BALB/c (H-2d) female mice with allogeneic spleen cells from C57BL/6 (H-2b) or CBA/H (H-2k) mice protects BALB/c offspring from graft-versus-host disease (GVH-D) following neonatal intraperitoneal inoculation of high doses of spleen cells respectively of C57BL/6 or CBA/H strains of mice. The mice survived GVH-D over one year after the allogeneic inoculum 24-48 h after birth and they did not show any signs of GVH reaction nor splenomegaly. We show that this phenomenon is antibody mediated and affects the developing immune system of the foetus. Repeated immunization of virgin female BALB/c with anti-H-2b or anti-H-2k antisera (Ab1) can equally abrogate GVH-D in their newborn offspring challenged at 24-48 h after birth with allogeneic spleen cells of H-2b or H-2k phenotype. Our results demonstrate that protection from GVH-D is not specific to the immunizing strain and occurs when the neonatal mice are challenged with C57BL/6 or CBA/H spleen cells. There is thus crossreactivity of tolerance against H-2 specificities. In this study we also report on the in vitro cellular immune responses of the surviving GVH-resistant mice and demonstrate that these responses against both the challenge and third party lymphocytes are impaired.

Animals↗

Characterization of two monoclonal antibodies raised against human testicular cells.

Human testicular cells isolated from biopsy tissue were used for generation of monoclonal antibodies. Two hybridoma supernatants C3 and D4 were selected according to their reaction with sperm-precursor cells (immature sperms) in an enzyme-linked immunosorbent assay (ELISA). C3 reacted with testicular but no other tissue. D4 did not reveal any pattern of testicular staining in spite of its similarity to C3 in binding to sperm-precursor cells in ELISA and microcytotoxicity test.

Adult↗