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Biomedical subjects

C S Reiss

Publications and source records attributed to C S Reiss.

At least 73 records · Page 4Linked to original sources
PubMed1984

Cytotoxic T lymphocyte recognition of class I H-2 antigens after DNA-mediated gene transfer.

Cytotoxic T lymphocyte (CTL) recognition sites on class I major histocompatibility complex molecules have been investigated by several laboratories by using cloned genes expressed on mouse L cells by DNA-mediated gene transfer. Recombinant genes, constructed by restriction endonuclease treatment of cloned H-2Dd and Ld genes and exchange of the N and C1 exons (exon shuffling) have provided an additional tool. These hybrid H-2 molecules expressed on L cells have been used as targets to achieve more precise localization of site(s) recognized by allospecific and virus-specific CTLs. CTL systems were chosen that limit recognition to either the Dd or Ld alloantigen or to virus and Dd or Ld complexes. Using this approach, we were able to map essential restricting site(s) to the N and/or C1 domains. Additional evidence is presented that the cytoplasmic tail of H-2 may be involved in interactions with some viral antigens and effect the formation of an immunogenic complex.

Animals↗
PubMed1984

Limiting dilution cultures reveal latent influenza virus-specific helper T cells in virus-primed mice.

Although lymphokine producing helper T cells are suspected to play an important role in the development of anti-viral cytotoxicity, they have not previously been demonstrable in influenza virus-primed mice unless the mice have first been pretreated with cyclophosphamide. It has been assumed that cyclophosphamide pretreatment was required to block the activities of suppressor cells which would otherwise interfere with helper T cell priming. We have developed a limiting dilution assay (LDA) for estimating influenza virus-specific T cell precursors for IL-2 secretion ("pHTL"), and have found that equal numbers of pHTL develop in virus-primed mice regardless of cyclophosphamide pretreatment. This result suggests that the cyclophosphamide-sensitive regulatory cells do not act in vivo to prevent helper cell priming, but rather act in vitro to oppose expression of helper cell activity. Comparison of helper cell function in conventional (high density) cultures and in LDA cultures reveals an Lyt-2+ cell which prevents development of cytotoxic function in conventional assays, but which fails to affect the outcome of the LDA experiments. We found that the pHTL population consists almost entirely of Lyt-2- cells, and that mice primed with the Type A strain, PR/8, develop pHTL responsive to a wide range of influenza viruses, including a Type B strain. Both results modify conclusions suggested by conventional assay methods. Since the LDA experiments seem to be relatively resistant to regulatory interactions which can influence the outcome of standard assay cultures, they can supply information about the characteristics of the pHTL itself that would otherwise be difficult to obtain.

Animals↗
PubMed1983

Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon.

We have used monoclonal antibody binding, measured by radioimmunoassay, fluorescence flow cytometry, and ultrastructural immunocytochemistry, to measure expression of Ia antigens on cultured human umbilical vein endothelial (HUVE) cells. Under standard culture conditions, HUVE cells do not express Ia antigens. However, treatment of primary HUVE cultures with phytohemagglutinin induces the expression of Ia antigens. Every endothelial cell in the culture becomes Ia-positive and endothelial cells appear to synthesize Ia. HLA-A,B is concomitantly increased. The expression of Ia appears to be mediated by T cells because (a) pretreatment of primary HUVE cultures with OKT3 plus complement blocks the action of the lectins but not of medium conditioned by lectin-activated peripheral blood mononuclear cells; (b) co-culture of endothelial cells with allogeneic T cells, in the absence of lectin, also induces endothelial Ia; and (c) human immune (gamma) interferon, produced by Chinese hamster ovary cells transfected with the human gamma interferon gene, directly induces endothelial Ia. During co-culture with lymphocytes, about one-third of the endothelial cells are Ia-positive after 24 h and all of the endothelial cells are Ia-positive by 72 h. Proliferation of allogeneic T cells starts by 96 h and peaks at 144 h. Thus, endothelial Ia appears sufficiently early to be a determinant for the proliferation of allogeneic T cells. Inducible expression of Ia by endothelium may be important both for allograft rejection and for recruitment of circulating T cells into the site of an immune response.

Cells, Cultured↗
PubMed1983

Allospecific and virus-specific cytolytic T lymphocytes are restricted to the N or C1 domain of H-2 antigens expressed on L cells after DNA-mediated gene transfer.

In order to identify the site(s) on major histocompatibility molecules recognized by cytolytic T lymphocytes (CTLs), the recognition of H-2 antigens expressed when cloned genes are introduced into mouse L cells by DNA-mediated gene transfer has come under investigation. Recently, recombinant H-2 genes have been constructed in vitro from restriction endonuclease fragments of cloned H-2Dd and H-2Ld genes which exchange the N and C1 external domains (exon shuffling). These hybrid H-2 genes direct the synthesis of hybrid H-2 antigens when introduced into L cells by DNA-mediated gene transfer. These transformed L cells have been used as target cells to achieve a more precise localization of the sites recognized by allospecific and virus-specific CTLs. CTL systems were chosen that allow one to probe allospecific Ld or Dd recognition or virus-restricted Ld or Dd recognition. Using this approach we were able to map essential CTL recognition sites to the N and C1 domains of class 1 molecules.

Animals↗
PubMed1983

Evidence for genetic restriction in the suppression of erythropoiesis by a unique subset of T lymphocytes in man.

The suppression of erythropoiesis by lymphocytes from patients with a T cell lymphoproliferative syndrome and pure erythrocyte aplasia has been previously demonstrated. To study the nature of the suppressor cell and possible genetic restriction of this suppression, we investigated a patient with severe anemia, splenomegaly, lymphocytosis, and erythroid aplasia. A 3-mo course of low-dose daily oral cyclophosphamide achieved a complete remission for over 12 mo. The surface phenotype of his lymphocytes was analyzed by means of antibodies to lineage, differentiation, and activation-specific surface antigens. The cells expressed mature T cell antigens T3, T8, and T11, while lacking T1. Immature T cell, B cell, and the monocyte-specific antigen Mo2 were absent, while Mo1, a monocyte-associated antigen not normally expressed on T cells, was present. T10 and Ia expressed as activation antigens were also present. The cells, cryopreserved at diagnosis, were thawed and co-cultured in plasma clot with patient remission marrow samples at T cell/bone marrow ratios of 1:1 and 2:1. There was nearly 90% suppression of erythroid colony-forming unit expression and 60% suppression of erythroid burst-forming unit expression at 2:1 T cell to bone marrow ratios and somewhat less suppression at 1:1. Granulocyte/macrophage progenitor expression was unaffected. Erythroid progenitor differentiation in the marrows of two HLA identical siblings was similarly suppressed. The cells were co-cultured with the marrows of nine nonrelated donors to investigate the potential genetic restriction of this suppression. Colony suppression equal to that observed in the marrow of the patient and his siblings was found in studies of two partially HLA identical individuals. No suppression was detected in marrow co-cultures of two entirely HLA dissimilar individuals. These results show that suppression of erythropoiesis by a unique subset of T8, Mo1, Ia-positive lymphocytes isolated from a patient with lymphocytosis and erythrocyte aplasia is genetically restricted.

Adult↗
PubMed1983

Cytotoxic T cells directed against HLA-DR antigens and their surface proteins.

The authors review their recent research involving the generation of cytotoxic T lymphocytes (CTL) directed against HLA-DR antigens. A mouse anti-human xenogeneic system first suggested that HLA-DR antigens could be recognized by CTL. Human allogeneic CTL specific for HLA-DR6 were generated and found to be OKT4+. The fact that these CTL were OKT4+ while anti HLA-A,B CTL were OKT8+ suggested that these T cell surface antigens may be involved in MHC antigen recognition; ie, they may be part of the T cell receptor. These OKT4+, HLA-DR specific CTL were further used to generate monoclonal antibodies (1) which block cytolysis and define novel antigens involved in the CTL-target interaction and (2) which define an antigenic complex on alloantigen activated T cells.

Animals↗
PubMed1982

Long-term human cytolytic T-cell lines allospecific for HLA-DR6 antigen are OKT4+.

Human allospecific cytotoxic T lymphocyte lines were established by weekly stimulation of peripheral blood lymphocytes with allogeneic Epstein-Barr virus-transformed lymphoblastoid cell lines in the presence of interleukin 2. The cytotoxic T lymphocyte lines were stimulated by either JY (which expresses HLA-A,B and -DR) or Daudi (which expresses HLA-DR but not -A,B antigens). Specificity of the effector cell lines was determined by antibody blocking and by patterns of cytolysis against a panel of target cell lines. The phenotype of the effector cells was identified by both negative (antibody and complement lysis) and positive (fluorescence-activated cell sorter) selection. The anti-JY lines only recognized targets bearing HLA-A2, B7 antigens and were composed exclusively of OKT4-8+ effector cells. The anti-Daudi lines, on the other hand, specifically recognized targets bearing DR6 and eventually contained only OKT4+8- cells. Thus, stimulation by Daudi cells can result in the generation of OKT4+ CTL lines that are allospecific for DR6 antigen.

Antigens, Surface↗
PubMed1982

Genetic control of the cytolytic T lymphocyte response to influenza viruses: H-2 genes influence the response to H-2Kb plus virus.

Genetic control of the cytolytic T lymphocyte responses to influenza virus was examined. Mice bearing the H-2b haplotype and F1 hybrid mice derived from C57BL/6 parents failed to recognize H-2Kb plus type A or type B influenza viruses. Congenic mice that shared H-2Kb but had either H-2Dd of H-2Dq genotypes responded in in vitro secondary cultures to H-2Kb plus virus. Mapping studies suggest the gene(s) controlling the ability to respond to H-2Kb plus virus can be localized in or near the H-2D region. Several interpretations of these observations are discussed.

Animals↗
PubMed1982

Specificity of OKT4+ cytotoxic T lymphocyte clones.

OKT4+, HLA-DR-specific CTL were cloned by limiting dilution, and two clones were evaluated. One clone, B8, specifically recognized DR6 antigens, whereas another cloned, C6, recognized an Ia-like determinant on some DR 3, 5, and 6 target cells. Both clones were OKT3+, OKT4+, and OKT8-, and their cytolysis could be blocked by OKT3 and OKT4, but not OKT8, antibodies. A panel of monoclonal antibodies that recognize DR molecules blocked target cell recognition by these OKT+ CTL. Although cloned B8 recognized a DR6-specific determinant, clone C6 appeared to recognize a supratypic determinant that may be common to some DR molecules (e.g., MT2) or possibly another human Ia-like antigen (e.g., SB). The availability of OKT+ CTL clones should help to dissect the Ia-like antigens recognized by human T cells.

Antibodies, Monoclonal↗
PubMed1982

Generation of long-term human cytolytic cell lines with persistent natural killer activity.

Human cell lines maintained by in vitro stimulation with the HLA-A, B-negative, DR-positive, Epstein Barr virus-transformed, lymphoblastoid cell line Daudi in the presence of conditioned medium demonstrated significant NK activity for over 6 wk in continuous culture. These cells lyse K562 and a broad panel of lymphoblastoid cell lines but do not lyse normal peripheral blood lymphocytes or pokeweed mitogen blasts. They possess the sheep red blood cell receptor but lack other T cell markers (Lyt-3+, OKT3-). Natural killer activity correlated with the presence of a Mac 1-positive subpopulation of cells present in these long-term lines.

Antibodies, Monoclonal↗
PubMed1981

Specificity of the helper T cell for the cytolytic T lymphocyte response to influenza viruses.

We have described a model system in which helper T cells are required to mount a primary antiviral cytolytic T lymphocyte response. The radioresistant helper cell can be found in the spleens of mice that have been immunized subcutaneously with influenza viruses 6-8 d previously. These helper cells appear to be type specific but cross-reactive among the subtypes of influenza A viruses. The phenotypes of the interacting cell populations were determined.

Antibody Specificity↗
PubMed1980

Development and characterization of allospecific long-term human cytolytic T-cell lines.

Two long-term human cytolytic T lymphocyte (CTL) lines (VE and JR), whose cytolytic activity was dependent upon both irradiated JY cells (the stimulating alloantigen) and T-cell growth factor, were established. These lines were monitored in culture for 6-8 months. Both lines were specific for HLA-A or B antigens or both and the JR line was allospecific for HLA-B7. These CTL lines killed specific target cells at an effector-to-target ratio of 0.4 (VE) or 0.08 (JR). All of the cells, which grow in suspension, rosetted with sheep erythrocytes and reacted with an antiserum specific for human T cells. The CTL line VE was used to raise rabbit antisera that immunoprecipitated two specific polypeptides (78,000 and 33,000 daltons) from labeled membranes of these CTL lines.

Animals↗
PubMed1980

Influenza type A virus M protein expression on infected cells is responsible for cross-reactive recognition by cytotoxic thymus-derived lymphocytes.

M protein of influenza A virus was detected with rabbit antiserum by both indirect immunofluorescence and by antibody plus complement-mediated cytolysis on the cell surfaces of both productively and nonproductively infected cells. In contrast, antiserum to nucleoprotein failed to react with unfixed infected cells, but did bind to fixed infected cells, especially in the perinuclear area. Incorporation of antiserum to M protein in a T-cell-mediated cytotoxicity assay produced almost complete abrogation of lysis of H-2-compatible cells infected with an influenza A virus of a subtype which differed from that used to elicit the cytotoxic T cells. However, the antibody did not significantly block 51Cr release from cells infected with the homotypic type A influenza virus. These observations are in accord with the hypothesis that the cross-reactive cytotoxic T-cell responses seen with cells infected by heterotypic influenza A viruses are due to recognition of a common M protein.

Animals↗
PubMed1980

Cellular immune responses of mice to influenza virus vaccines.

Parenteral sensitization of mice with equivalent amounts of untreated, gradient-purified or UV-inactivated influenza A/PR/8/34 virus (PR8 virus) results in the stimulation of maximal serum antibody titers, greatest numbers of antibody-forming cells (AFC), and strong virus-specific cytotoxic T lymphocyte (CTL) activity. In contrast, inoculation of formalin-inactivated virus, which induced antibody titers of equivalent magnitude, did not elicit a measurable primary CTL response nor prime for a secondary response. However, in mice previously exposed to untreated virus, challenge with formalin-inactivated virus evoked a secondary CTL response. Immunization of unprimed mice with aggregated viral glycoproteins or detergent-disrupted virus vaccine was much less immunogenic for antibody and AFC responses and did not evoke measurable primary, secondary, or memory cytotoxic effector cells in vivo.

Animals↗
PubMedDate not supplied

IL-12 and viral infections.

Interleukin-12 activates natural killer cells and promotes the differentiation of Th1 CD4+ cells; it is a critical factor in viral immunity. IL-12 is secreted by antigen presenting cells including dendritic cells, macrophages and astrocytes, both in tissues and in secondary lymphoid organs. Experimental studies have shown that administration of the cytokine rapidly activates both innate and specific immune responses; this results in enhanced host cellular responses and generally, promotes clearance of virus and host recovery from infection. The observations of many laboratories, studying viral immunity to both RNA and DNA based pathogens, are summarized.

Animals↗
PubMedDate not supplied

Lymphocytes recognize human vascular endothelial and dermal fibroblast Ia antigens induced by recombinant immune interferon.

T-lymphocyte-mediated responses to the cellular components of blood vessels are important in rejection of allografts. The induction of cytolytic T lymphocytes (CTLs) depends on recognition of foreign class II major histocompatibility complex antigens (human HLA-DR, DC/DS, SB and others, collectively referred to as Ia) on the target cells whereas killing by CTLs usually depends on recognition of foreign class I antigens (HLA-A, B), although some alloreactive CTLs recognize foreign Ia instead of HLA-A, B (refs 5-8). The expression of Ia antigens has traditionally been regarded as restricted to immunological cell types, and the presence of class II antigen-bearing 'passenger' leukocytes in rodent organ grafts appears necessary for graft rejection. Recently, Ia antigens have been observed by immunofluorescence microscopy on human renal and dermal capillary endothelium. We have previously shown that human umbilical vein endothelial (HUVE) cells in standard culture conditions do not bear Ia antigens, but may be induced to do so by products of lectin- or alloantigen-activated T lymphocytes. Furthermore, we found that recombinant immune interferon (IFN-gamma), free of other lymphokines, is a potent inducer of Ia expression in HUVE cells. Here we report that IFN-gamma also induces Ia expression on human foreskin capillary endothelial (HFCE) cells, HUVE cells transformed by Simian virus 40 viral DNA (SV-HUVE cells) and human dermal fibroblast (HDF) cells in culture. Further, we present evidence that Ia present on HUVE cells and HDF cells can be functionally recognized by human T cells, resulting in a two-way interaction between T cells and mesenchymal cells that may be important in allograft rejection.

Cells, Cultured↗
PubMedDate not supplied

Construction, expression and recognition of an H-2 molecule lacking its carboxyl terminus.

A mouse major histocompatibility antigen (H-2) gene, encoding a novel H-2Ld molecule lacking its intracytoplasmic domain, has been constructed and introduced into mouse L-cells. The novel H-2 molecule is found on the surface of the transfected cells at the same level as L-cells transfected with the native H-2Ld gene. Allo- and influenza-specific cytotoxic T lymphocytes can recognize the truncated H-2 gene product nearly as efficiently as the normal H-2Ld gene product. However, vesicular stomatitis virus-specific cytotoxic T lymphocytes recognize the truncated H-2Ld molecule less efficiently than the complete H-2Ld product. The rate of capping of the truncated H-2Ld molecule was investigated and found to be the same as that of the complete H-2Ld gene product.

Amino Acid Sequence↗