Search PubMed⌕ Search

Biomedical subjects

E Simpson

Publications and source records attributed to E Simpson.

At least 199 records · Page 11Linked to original sources
PubMed1981

Generation of effector cells from T cell subsets. III. Synergy between Lyt-1 and Lyt-123/23 lymphocytes in the generation of H-2-restricted and alloreactive cytotoxic T cell.

Lyt-123/23 and Lyt-1 T cell subsets, positively selected by separation on the fluorescence-activated cell sorter, were tested in vitro for their role in the generation of H-2-restricted and alloreactive cytotoxic T cells. It is shown that in the proliferation assay, both T cell subsets responded equally well to H-2 and non-H-2 antigens (H-Y), respectively. In contrast, none of the selected Lyt subsets, but only the mixed population containing Lyt-1 and Lyt-123/23 lymphocytes gave rise to both H-2-restricted (anti H-Y, anti-trinitrophenyl) and alloreactive (anti-H-2) cytotoxic lymphocytes. The data imply an essential role of Lyt-1 cells as inducers or helpers in the generation of all cytotoxic lymphocytes from their precursors in the Lyt-123/23 pool.

Animals↗
PubMed1981

Functional and binding activity of monoclonal anti-Thy-1 antibodies: evidence for different expression of the two alleles.

Monoclonal anti-Thy-1.1 and anti-Thy-1.2 antisera selected for complement-dependent cytotoxicity have high cytotoxic and binding titers on thymocytes and peripheral T cells of mouse strains bearing the appropriate Thy-1 allele. The effect of both anti-Thy=1.1 and anti-Thy-1.2 monoclonal antisera plus complement on cytoxic T cell effectors is to abrogate their activity. On the functional activity of precursor cytotoxic T cells, monoclonal antisera against the two alleles have different effects: anti-Thy1.2 plus complement removes precursor activity of Thy-1.2-bearing strains, including (Thy-1.1 X Thy-1.2) F heterozygotes, In contrast, six different anti-Thy-1.1 monoclonals, including four of the IgM class and two of the IgG class, failed to remove cytotoxic precursor activity from the splenic T cells of AKR, A. Thy-1.1 or (CBA X AKR) F1 mice. Analysis by florescence-activated cell sorting of in vitro cultured AKR spleen cells shows that Thy-1.1 antigen appears on the cel surface during the five-day culture period.

Alleles↗
PubMed1981

Analysis of haplotype preference in the cytotoxic T-cell response to H-Y.

The mechanisms determining which parental haplotype is selected in (CBA X B10) (k X b)F1 female mice for major histocompatibility complex (H-2) restricted, male-specific (H-Y), immune, cytotoxic T-cell (Tc-cell) responses, was investigated. The data show that haplotype preference is variable, and may be directed towards one, both, or neither of the parental haplotypes. This preference is reflected in the precursor or frequency of memory Tc cells as measured by limiting dilution assays. It was further shown that maternal influence, antigen dose, route of immunization, and a feedback mechanism on the stimulator cells in vivo could not influence haplotype preference or its observed variability. Evidence for cross-reactive killing by H-2k and H-2b H-Y immune Tc cells on H-2b and H-2k allogeneic targets, respectively,, (i.e., the independent haplotype of the other parent of the F1 mice), provide evidence for natural tolerance as a possible mechanism to explain haplotype preference.

Animals↗
PubMed1981

T-cell hybridomas producing hapten-specific suppressor factors.

We have made several T-T hybridomas which secrete soluble factors capable of suppressing an in vitro antibody response to nitrophenol (NP), but not other unrelated antigens. These factors bind specifically to NP, and express determinants coded for in the I-J region of the mouse major histocompatibility complex. No determinants that cross-react with the constant regions of mouse immunoglobulins are present on the factors. Three sub-clones originating from the same initial culture well of hybridoma cells secrete factors which carry I-J determinants of different haplotypes. One clone expresses I-J determinants derived from the suppressor cell parent, another expresses I-J determinants derived from the tumour cell parent, and a third expresses both. This correlates exactly with I-J determinants expressed on the cell membrane, and suggests the participation of at least two genes in the determination of suppressor-factor structure.

Animals↗
PubMed1980

Delayed-type hypersensitivity responses to H-Y: characterization and mapping of Ir genes.

This paper examines the delayed-type hypersensitivity (DTH) response to male (H-Y) antigen(s). Female mice of the H-2b haplotype developed delayed footpad reaction to syngeneic or allogenic male thymus and spleen cells after priming with syngeneic male thymus and spleen cells. The reaction peaks at 24 h, has classical DTH histology and is specific to H-Y antigen as it is not elicited with female cells. Cell transfer studies show that donor/recipient matching at the I-Bb subregion is necessary for successful transfer of DTH and that the effective primed population is Thy-1+, Lyt-1+, 2-. DTH response to H-Y antigen appears to be confined to mice of the H-2b haplotype. There appears to be a lack of associative recognition between H-Y antigen and MHC-coded determinants in the effector phase of DTH, and macrophage processing of H-Y seems likely, since nonresponder haplotypes can elicit the DTH response. Studies with H-2b recombinant mouse strains indicate that the dominant Ir gene is located in the I-B region. Female F1 hybrid mice derived from matings of strains not involving H-2b haplotype failed to develop DTH to H-Y. In summary, these data imply that a complete correlation exists between DTH to H-Y and the ability to reject male skin graft, suggesting that the effector mechanisms of skin-graft rejection may closely involve DTH cells.

Animals↗
PubMed1980

Allogeneic tolerance in embryo aggregation mouse chimeras studied by mixed lymphocyte culture and cell-mediated lympholysis.

Tolerance in embryo aggregation (EA) mouse chimeras was investigated using mixed lymphocyte culture (MLC) reaction and cell-mediated lympholysis (CML). In most cases, spleen or lymph node cells from EA chimeras were specifically unresponsive toward their parental cells in both MLC and CML. There was no evidence to support the involvement of "serum-blocking factors" or suppressor cells under these experimental conditions. There was, however, an exceptional chimera in which cytotoxic T cell percursors reactive against one parental cell may have been present. We argue for classical clonal elimination being the primary mechanism for tolerance in EA chimeras and discuss a role of suppressor mechanisms for self-tolerance.

Animals↗
PubMed1980

Calcium metabolism in a fatal case of sodium fluoride poisoning.

A patient was admitted to a district general hospital within an hour of ingesting a fatal dose of sodium fluoride. The results of laboratory investigations, together with some in vitro findings, support the hypothesis that the hypocalcaemia of fluoride poisoning is the result of fluorapatite formation and not calcium fluoride precipitation, and that its persistence reflects the severity of the calcium deficit and not an inhibitoin of normal homeostatic mechanisms. It is suggested that the role of renal clearance of fluoride may be more important than had been realised hitherto.

Apatites↗
PubMed1979

Expression of Ly-6 alloantigen during differentiation of cytotoxic T cells.

We have prepared anti-Ly-6.2 by immunization of (CBA/Ca X A-Thy-1a)F1 with AKR/Crc lymphocytes and used the antiserum to study heterogencity of peripheral T lymphocytes. The Ly-6 alloantigen is found on all activated cytotoxic T cells studied, directed to a variety of different target antigens. The antiserum reveals heterogeneity among the precursors of T killer cells, i.e. allogeneic precursors are Ly-6-, whereas the generation of cytotoxic cells to hapten-modified syngeneic cells and xenogeneic cells is partially abrogated by serum pretreatment. Precursors of some in vivo primed responses are also Ly-6+. These findings indicate that the expression of Ly-6 antigen is, at least, partially related to the stage of T cell activation. The in vitro proliferative response of T cells to allogeneic Ia antigens is substantially reduced by pretreatment with anti-Ly-6.2 serum suggesting that this antiserum may be a useful tool for the study of heterogeneity in the Ly-1+ pool of T cells.

Animals↗
PubMed1979

Use and functional properties of peripheral blood lymphocytes in mice.

Peripheral blood lymphocytes (PBL) were isolated and examined for their ability to respond in vitro to H-2 and H-Y antigens and also to hapten conjugated syngeneic cells. In addition, these lymphocytes were tested as antigen and target cells in in vitro mixed lymphocyte reaction and in chromium release cell mediated lympholysis respectively, as well as serving as targets for the H-2 typing of chimeric mice. Two methods were used to isolate the lymphocytes: a density gradient separation and a double water lysis technique. PBL, prepared by either method compared favourably with splenic lymphocytes in all aspects of anti-H-2 cytotoxicity but could not be used as responder for anti-H-Y cytotoxicity. In addition a method has been developed using PBL as targets for H-2 typing of both allophenic and irradiation chimeric mice. The small numbers of cells required for each of these procedures allows for the preselection of suitable mice and/or multiple experimental determinations on individual mice.

Animals↗
PubMed1978

Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses.

Cross-reactive T-cell cytotoxicity is seen when cytotoxic responses are generated in mixed lymphocyte cultures either between mouse strans which differ at the major histocompatibility complex, H-2, or between H-2b mutant strains and the strain from which they were derived. This cross-reactivity can be measured with [51Cr] labeled target cells from a number of different H-2 haplotypes, and the pattern of cross-reaction indicates that the target antigens are unlikely to be any of the serologically defined public specificities. In contrast, the specificity of H-2 restricted cytotoxic responses, such as that to the male-specific antigen, H-Y, is exquisite, and male cells from strains of mice carrying H-2 haplotypes other than the responder have never been found to act as appropriate targets. The contrast between the specificity of anti-H-2 and H-2 restricted responses may argue for a greater idiotypic homogeneity of the cells makiing H-2 restricted responses, and the greater specificity of these responses may be necessary for their biological function.

Animals↗