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Biomedical subjects

E Simpson

Publications and source records attributed to E Simpson.

At least 235 records · Page 13Linked to original sources
PubMed1977

Responsiveness to HY antigen Ir gene complementation and target cell specificity.

The H-2 restricted nature of the cytotoxic T cell responses to the HY antigen in mice has been reviewed, together with mapping data for the H-2 K and/or D association of responses to male cells of the following haplotypes: H-2b, H-2d, H-2k, H-2s. Ir gene complementation is implicated in the HY response of a number of F1 mice derived from non-responder parental haplotypes, and in one recombinant strain. Thus, at least two and possibly more Ir genes are involved in the anti-HY response, in addition to the K and/or D gene products with which HY is obligatorily associated, certainly at the target cell level.

Animals↗
PubMed1977

Fractionation of lymphocytes involved in the generation of cell-mediated cytotoxicity over insolubilized conjugated histamine columns.

Spleen cells from normal BALB/c mice were cultured in vitro with irradiated C57BL/6 stimulating cells. Five days later the T cell-mediated cytotoxic activity of the effector cells was assessed with a 51Cr-release assay that used H-2bEL-4 tumor cells as targets. Before the BALB/c responding lymphocytes were sensitized they were fractionated by passing the spleen cells over insolubilized histamine rabbit serum albumin Sepharose columns (H-RSA-S) or over rabbit serum albumin Sepharose (RSA-S) control columns. Fractionation of cells over the H-RSA-S columns depleted or significantly reduced the cytotoxic potential of the unretained cells. All cytotoxic potential was recovered when the cells that adhered to the H-RSA-S were eluted from the columns. In contrast, no effect on responsiveness was detected after the cells had been fractionated over the control column. The loss of response potential by the cells that did not adhere to H-RSA-S could not be accounted for by removal of macrophages nor by the concentration of cells with suppressor activity in the effluent. These cell fractionation studies raise the possiblity but do not prove that cytotoxic precursor cells may express amine receptors that could be responsible for their retention by insolubilized histamine columns.

Animals↗
PubMed1976

The effect of allogeneic presensitization on H-Y graft survival and in vitro cell-mediated responses to H-y antigen.

C57BL/6 and C57BL/10 female mice were grafted with skin from male or female donors incompatible for H-2 and/or non-H-2 antigens. Syngeneic male grafts applied after the rejection of primary allografts or syngeneic male grafts were rejected in accelerated (second set) fashion, whereas male grafts applied after primary female grafts were not. In addition, C57BL/10 female spleen cells, primed in vivo with an allogeneic (BALB/c, CBA, or B10.BR) male graft and challenged in vitro in mixed lymphocyte culture with syngeneic (C57BL/10) male cells, produced cytotoxic cells specific for syngeneic male target cells. We conclude that at least some component of H-Y is detected by female responder cells on allogeneic male cells, and that the second set cell mediated response to H-Y is not necessarily restricted by the H-2 haplotype of the primary sensitizing strain. Moreover, (CBA X B10) F1 females, primed in vivo with male cells of one parental haplotype (B10 or CBA) and challenged in vitro with male cells of the other parental haplotype (CBA or B10), fail to lyse male target cells of either parental haplotype. It therefore seems unlikely that a helper determinant shared between B10 and CBA is sufficient to explain the ability of CBA male cells to prime H-2-restricted T-cell cytotoxic responses by B10 females.

Animals↗
PubMed1976

The differentiation of cytotoxic T lymphocytes in vitro: an ultrastructural study.

T killer cells were identified morphologically in two different culture systems. The first system allowed identification by comparing under identical culture conditions two types of stimulation, one leading to cytotoxic activity levels that were very high (H-2 stimulation) and the other to levels which were practically nil (M-locus stimulation). A second system allowed identification by the use of a collaborative system in which relatively pure precursors of T killer cells were mixed with precursors of T amplifier cells from which they were distinguishable by their Thy-l antigen. In this latter case, surface labelling techniques had to be used. As in the in vivo situation, T killer cells were medium-sized pale cells with evidence of a well-developed secretory and motile apparatus. No evidence of highly active protein synthesis was found. Other T cells were dark and mainly derived from the T amplifier population, again consistent with in vivo findings. There was considerable background proliferation, even in the absence of any added antigen, and this included the formation of some well-developed plasma cells.

Animals↗
PubMed1976

Micromethods for induction and assay of mouse mixed lymphocyte reactions and cytotoxicity.

A new method in which induction of mixed lymphocyte responses and cytotoxicity can be performed under identical conditions is described. This enables the investigation of the relationship between MLR and cytotoxicity. A micro method for the 51Cr release assay for cytotoxicity is described using both mitogen-induced blasts and tumors as target cells. Under the conditions used data obtained is suitable for linear regression analysis, enabling quantitative comparisons to be made.

Animals↗
PubMed1976

Stimulation of mixed lymphocyte cultures and cytotoxic responses: evidence that T cells express SD but not LD antigens, whereas B cells express both.

By separating T and B cells from stimulator spleens it has been found that mixed lymphocyte response (MLR) and cytotoxic cells are generated in responder T cell populations by B but not by T stimulator cells in a wide variety of strain combinations. It is suggested that MLR-stimulating or LD antigens are expressed on B but not T cells, and that their presence is necessary in order to generate cototoxic responses to H-2K and/or H-2D (or SD) antigens which are present on both T and B cells. The finding that B cells and macrophages stimulate MLR is consistent with the hypothesis that Ia antigens, expressed on both these cell types but not on nylon column purified peripheral T cells, are the MLR-stimulating or LD determinants.

Animals↗
PubMed1976

Immunological reactivity of B mice reconstituted with various numbers of syngeneic bone marrow cells.

Adult thymectomized mice were sublethally irradiated and reconstituted with various doses of syngeneic bone marrow. Immunological reactivity was assessed by allogeneic skin grafting at various intervals after reconstitution. It was found that reconstitution with high doses (1 X 10(7), 2 X 10(7)) of bone marrow was associated with an ability to reject allogeneic skin grafts and that this reactivity increased with time. Following rejection of a first skin graft, second grafts were rejected in an accelerated manner. These mice had measurable levels of Thy 1.2 positive cells in the spleen. In contrast, low-dose bone marrow reconstitution (1 X 10(6), 2 X10(6)) produced mice which did not reject either first or second allogeneic skin grafts, and such mice had at most only very low levels of Thy 1.2 positive cells in their spleens.

Animals↗
PubMed1975

In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice.

C57BL/10 female mice were primed to the male specific antigen H-Y, either by grafting with syngeneic male tail skin or by i.p. injection of syngeneic male spleen cells. Primed female spleen cells, either unseparated or filtered through nylon wool to remove most of the B lymphocytes, were then cultured for 5 days in vitro with irradiated syngeneic male spleen cells and assayed against 51Cr-labeled target cells. Both unseparated and nylon wool filtered female cells displayed significant cytotoxic activity restricted to male target cells. Pretreatment of sensitized female cells with antitheta serum and complement just before assay abolished cytotoxic responses. We were unable to demonstrate cell-mediated cytotoxic responses into two nonresponding strains, CBA and B10.A, which fail to reject male isografts. The cytotoxic activity of C57BL/10 female cells was restricted to male target cells histocompatible with C57BL/10 over at least a portion of the major (H-2) histocompatibility complex. We conclude that secondary in vitro cytotoxic responses against the H-Y antigen are mediated by cytotoxic T lymphocytes, and that the H-Y target cell antigen may be specified by the H-2 complex.

Animals↗
PubMed1975

Regulation of the immune response by subclasses of T lymphocytes. I. Interactions between pre-killer T cells and regulatory T cells obtained from peripheral lymphoid tissues of mice.

The generation of killer cells to alloantigens in vitro depends upon an interaction between two subclasses of peripheral T cells: "pre-killer" T cells and "regulatory" T cells. The pre-killer T cell, found in highest concentrations in peripheral lymph nodes of mice, is sensitive in vivo to the administration of small doses of anti-thymocyte serum (ATS) and is depleted in vitro by treatment with (a) anti-Thy-1.2 + C, (b) low doses (600 r) of x-irradiation. Specificity of pre-killer cells is supported by adsorption of pre-killer activity on appropriate allogeneic monolayers and by the specific absence of this activity from lymphoid tissues of mice rendered tolerant in neonatal life. Although T cells remaining in the spleen 2 days after a small dose of ATS (SPA-T) did not generate killer cells, this subset exerted substantial regulatory effects upon the generation of killer activity by pre-killer T cells. The addition of this population of regulatory T cells to small numbers of lymph node T cells (LN-T) resulted in substantial enhancement in the generation of killer cells from the LN-T pre-killers. The addition of SPA-T to larger numbers of LN-T (which produce strong responses alone), failed to enhance the response, and in some cases resulted in significant suppression which could not easily be accounted for by alteration in cell numbers in culture. Although amplifier activity was relatively radioresistant, "suppressor" activity was sensitive to relatively small doses of irradiation. The significance of this T-T interaction is discussed.

Animals↗
PubMed1975

Regulation of the immune response by subclasses of T lymphocytes. II. The effect of adult thymectomy upon humoral and cellular responses in mice.

The immunologic consequences resulting from thymectomy in adult life were investigated. Primary humoral responses were not diminished shortly after adult thymectomy, as judged by responses of intact thymectomized mice as well as by the ability of spleen cells from such mice to transfer primary responses. However, secondary humoral responses were substantially reduced in irradiated recipients of spleen cells from primed adult-thymectomized mice, suggesting that the thymus is required in adult life to maintain a population of cells important in the generation of immunologic helper memory. By contrast, small doses of anti-thymocyte serum, which primarily affect recirulating T cells, abrogated the primary humoral response, but allowed the subsequent development of immune memory. Using a technique permitting in vitro sensitization of purified T cells to alloantigens, it was shown that adult thymectomy increases the ability of T cells to generate primary cytotoxic responses, but had little effect upon the development of cytotoxic T memory activity. These experiments suggest that in adult life the thymus maintains a regulatory population of T cells in peripheral tissues which suppress early T cell differentiation to cytotoxic effector cells and potentiates the development of immune memory.

Age Factors↗