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G H Sunshine

Publications and source records attributed to G H Sunshine.

At least 37 records · Page 2Linked to original sources
PubMed1984

Antigen-presenting cells do not discriminate between self and nonself.

The immune response to F protein in mice provides a system in which the capacity of antigen-presenting cells to present autologous protein to T cells can be examined. When we used the F-type 1 (F.1) and F-type 2 (F.2) combination, these cells proved equally able to present autologous and foreign protein in both an in vivo adoptive transfer and an in vitro proliferation assay. This formally excludes the possibility that these cells themselves discriminate between self and nonself, while still allowing the possibility that their uptake of antigen may be regulated by lymphocyte products.

Animals↗
PubMed1984

Requirements for suppressor T cell activation.

Third-order (Ts3) suppressor cells are generated after conventional immunization. These cells, however, will not mediate suppressor cell function unless specifically triggered by an activating signal, termed TsF2. This report analyzes the mechanism of this TsF2-mediated triggering event. TsF2-mediated suppression is genetically restricted by genes in the I-J and Igh-V regions. The target of the I-J restrictions is a firmly adherent accessory cell, which appears to express I-J-related determinants. These accessory cells are sensitive to cyclophosphamide treatment and 500 R irradiation. In contrast, the target of the Igh-V restriction of TsF2 appears to be the Ts3 cell, which carries antigen-specific, idiotype-related receptors. The mechanism of suppressor cell activation appears to involve two stages. Presentation of I-J-restricted TsF2 by I-J-compatible presenting cells and a second step involving idiotype-anti-idiotype interactions between TsF2 and the Ts3 cell. I-J compatibility is not required with the accessory cell for Ts3 activation. Finally, we hypothesize that the anti-idiotypic determinants expressed on TsF2 can serve as an internal image of antigen, thereby permitting specific targeting of the factor.

Animals↗
PubMed1984

A role for macrophages in suppressor cell induction.

A mechanism responsible for the induction of NP-specific first order (inducer) suppressor cells (TS1) is described. TS1 cells are induced by i.v. administration of hapten-coupled splenic cells. Their activity is assessed by the adoptive transfer of NP-specific suppression during the afferent phase of the contact sensitivity response. NP-coupled firmly adherent, FcR+, I-A-bearing macrophages induce TS1. The antigen-presenting cells required for TS1 induction lack the Thy-1 and Lyt-1 markers, and are resistant to 500 R irradiation and to cyclophosphamide treatment. NP-coupled dendritic cells fail to induce TS1 activity. The induction of TS1 cells is genetically restricted by genes that map in the I-J region of the H-2 complex. The NP-coupled antigen-presenting cells must share at least one I-J allele with the TS1 donor for effective induction of TS1 activity. To minimize allogeneic effects in these studies, the activity of the TS1 population was assessed by adoptive transfer into syngeneic recipients. The present results are compared with the mechanisms required for the induction of second and third order suppressor cells.

Animals↗
PubMed1983

Mouse spleen dendritic cells present soluble antigens to antigen-specific T cell hybridomas.

In the presence of the soluble polypeptide antigens ovalbumin and keyhole limpet hemocyanin, purified mouse spleen dendritic cells induce the secretion of IL-2 by antigen-specific T cell hybridomas. This response is H-2 restricted and can be specifically inhibited by monoclonal anti-I-A. These data indicate that dendritic cells can present soluble antigen to H-2-compatible T cells.

Animals↗
PubMed1983

Stimulator cell requirements for allospecific T cell subsets: specialized accessory cells are required to activate helper but not cytolytic T lymphocyte precursors.

Murine cortisone-resistant thymocytes were separated by staining with monoclonal anti-Lyt-2 antibody and FMF into Lyt-2- and Lyt-2+ subsets in order to analyze the nature of stimulator accessory cells required to activate each of these functionally distinct T cell subpopulations. The Lyt-2- fraction was able to proliferate but not to generate cytotoxic cells when stimulated by irradiated allogeneic spleen cells. Fractionation of the stimulator population showed that low numbers of dendritic cells and splenic macrophages, but not equivalent numbers of whole spleen cells or peritoneal macrophages, were able to stimulate the Lyt-2- population. On the other hand, the Lyt-2+ population, which showed little if any proliferation in response to irradiated spleen cells, contained all the precursors of cytolytic T lymphocytes. In contrast to the highly specific stimulator requirement of the Lyt-2- fraction, allospecific cytotoxic cells were generated from Lyt-2+ cells by any alloantigen-bearing stimulator cell provided interleukin 2 was present. This was confirmed by limiting dilution analysis: alloreactive CTL-P frequencies in spleen and thymus were not influenced by the nature of the stimulator cell. These data collectively indicate that heterogeneous Ia+ accessory cells are required to stimulate helper but not cytolytic T cell precursors.

Animals↗
PubMed1982

Heterogeneity of stimulator cells in the murine mixed leukocyte response.

Mouse spleen cells were fractionated and tested for their ability to stimulate a primary mixed leukocyte response (MLR). Several nonlymphoid populations were stimulatory, purified dendritic cells and 18-h adherent macrophages being the most effective. B and T lymphocytes and peritoneal washout cells were almost ineffective by comparison. This hierarchy of stimulator potential was observed whether the genetic difference between stimulator and responder was whole H-2 or H-2 subregion (K, D, I, I-J). Allostimulatory populations contained a high proportion of cells expressing I region determinants. The functional importance of these antigens was confirmed using specific anti-I region antisera. Thus, it appears that stimulator cells in the MLR are heterogeneous, Ia-bearing, and of "accessory" rather than lymphoid type.

Animals↗
PubMed1982

Alloreactive cytotoxic T lymphocyte responses to H-2 products on purified accessory cells.

Several purified accessory cell populations were examined for their capacity to stimulate allospecific cytotoxic T lymphocytes (CTL). A number of non-lymphoid accessory cells stimulated CTL directed against the whole H-2 region and to isolated Class I or Class II products of the major histocompatibility complex (MHC). The accessory cells which stimulated CTL expressed surface Ia. The generation of CTL to Class I MHC products could be inhibited by antisera directed at Class II molecules on the same accessory stimulator cell surface. These findings demonstrate the importance of Class II MHC products on heterogeneous accessory cells capable of stimulating alloreactive CTL.

Animals↗
PubMed1982

In vitro responses to the liver antigen F.

In this paper we describe the first in vitro response to the liver alloantigen F. The anti-F response serves as a valuable model for autoimmune phenomena since priming appropriate strains of mice (responders) with allogeneic but not syngeneic type F leads to autoantibody production. The in vitro system is based on the proliferation of T cells, from mice primed in vivo with F, when coincubated with splenic adherent cells (SAC) prepulsed with F in vivo. The system displays two important correlates of the in vivo antibody response to F:1.T cells from mice primed with syngeneic F do not proliferate when incubated with SAC prepulsed with syngeneic F and 2. Mice that do not make antibody responses to allo F in vivo (DBA/2) do not show in vitro proliferative responses. These findings indicate that the proliferative assay is a good in vitro model for the F response.

Animals↗
PubMed1980

Dendritic cells induce T cell proliferation to synthetic antigens under Ir gene control.

Dendritic cells prepared by a modification of the method of Steinman and Cohn are I-A+ and FcR-. They are extremely potent at activating not only allogeneic T cell proliferation but also antigen-specific syngeneic T cell proliferation. Dendritic cells from nonresponder strains are unable to present antigens to responder X nonresponder T cells, suggesting that they may be a site of Ir gene product expression.

Animals↗
PubMed1978

Thymopoietin enhances the allogeneic response and cyclic GMP levels of mouse peripheral, thymus-derived lymphocytes.

The action of the purified thymic factor, thymopoietin, on populations of post-thymic lymphocytes has been studied. Thymopoietin, at concentrations as low as 1.5 ng/ml, uniquely enhanced the proliferative response of peripheral T cells from lymph node and spleen to allogeneic stimulation. Enhancement of the allogeneic response (MLR) was not produced by several polypeptide hormones, including insulin, ACTH, HCG, or Ubiquitin. Treatment of spleen cells with anti-Thy-1 antiserum almost completely abolished the MLR. Thymopoietin's stimulatory effects could not reverse this. Thymopoietin treatment of Thy-1+-enriched spleen cell populations enhanced the MLR even when thymopoietin was removed as early as 2 min after incubation with responding cells. The interaction of thymopoietin with peripheral Thy-1+ cell populations produced a rapid and transient rise in cyclic GMP levels and slightly decreased cyclic AMP levels. These results suggest that thymopoietin interacts with one or more Thy-1+ subpopulations and that this interaction involves early changes in cyclic nucleotide metabolism.

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