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M F Lipscomb

Publications and source records attributed to M F Lipscomb.

65 records · Page 4Linked to original sources
PubMed1981

Biochemical characterization of Ia alloantigens in guinea pigs. I. Synthesis of Ia antigens by subsets enriched for B cells, T cells, or macrophages.

Peritoneal exudate cells from immune guinea pigs consist primarily of T lymphocytes (PEL) and M phi. After selection of PEL from animals immunized with ovalbumin by culture on specific antigen-pulsed syngeneic M phi, recovered T cells (selected PEL) are 75 to 95% Ia+ by both cytotoxicity and immunofluorescent analysis on the FACS using alloantisera to Ia from guinea pigs or mice. The subunit structure of the Ia molecules on T cells is similar to that of Ia molecules obtained from B cells, as determined by radiolabeling, immunoprecipitation, and analysis of gels. Incorporation of labeled amino acids into Ia by selected PEL was shown to be due to T cells because of the lack of effect of depletion of Ig+ cells, the elimination of incorporation with a monoclonal anti-lymphocyte antibody, and the negligible increase in radioactive Ia after addition of large numbers of peritoneal exudate M phi. Furthermore, when F1 (2 x 3) PEL are selected on parental M phi, the selected PEL express both parental (2 and 13) Ia specificities, which suggests that the Ia molecules are not adsorbed by T cells after their release by M phi. Evidence that synthesis by splenocytes is due to B cells was obtained by the results of deletion experiments with alpha Ig and C. Similarly, synthesis of Ia by populations of pulmonary alveolar M phi, which contain greater than 98% M phi as judged by morphology, adherence, and latex ingestion, was demonstrated to be due to M phi because of the lack of effect of removing T and B cells.

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PubMed1981

Antigen presentation by guinea pig alveolar macrophages.

The role of alveolar macrophages (M phi) in the induction of immune responses within the lung was investigated. Guinea pig alveolar M phi obtained from bronchoalveolar cells (BAC) were found to function as well as peritoneal exudate M phi in supporting proliferation of purified lymph node lymphocytes (LNL) induced by both soluble antigens and mitogen (Con A). Several lines of evidence indicate that the alveolar M phi is an effective antigen-presenting cell. 1) Washed alveolar M phi, previously "pulsed" with antigen, replaced both soluble antigen and BAC in the stimulation of immune LNL. 2) The interaction of alveolar M phi, over 80% of which were Ia positive, with lymphocytes was genetically restricted, i.e., only antigen-pulsed alveolar M phi that shared I region-encoded antigens with the antigen-specific T lymphocytes stimulated their proliferation. Furthermore, removal of Ia-positive alveolar M phi abrogated this response. 3) Antigen-pulsed alveolar M phi specifically bound immune T lymphocytes. In contrast, no evidence was obtained for immunosuppression by alveolar M phi. Thus, alveolar M phi failed to suppress specific LNL proliferation even at ratios of alveolar M phi to LNL of greater than 20:1, ratios that often exist locally within the lung. The possible role of antigen-bearing alveolar M phi in inducing local immunity and also in focusing a systemic response are discussed.

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PubMed1979

Specific binding of T lymphocytes to macrophages IV. Dependence on cations, temperature and cytochalasin B-sensitive mechanisms.

Peritoneal exudate lymphocytes (PEL) from immune guinea pigs adhere to macrophages carrying the relevant antigen and are thereby stimulated to proliferate in culture. The resultant PEL represent a population highly enriched with regard to their capacity to specifically rebind to antigen-pulsed macrophages. We have studied the mechanisms underlying specific binding of lymphocytes to macrophages by examining the effects of physical and chemical modifications of the two cell types. Specific binding was inhibited by fixation of cells, metabolic inhibitors, low temperatures, cytochalasin B and divalent cation depletion. After specific binding has taken place, cation depletion, but not cytochalasin B or low temperatures, disrupts binding. These observations indicate that specific binding occurs by a series of discrete events that can be operationally distinguished.

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PubMed1978

Specific binding of T lymphocytes to macrophages. III. Spontaneous dissociation of T cells from antigen-pulsed macrophages.

Peritoneal exudate lymphocytes (PEL) from immune guinea pigs that adhere to antigen-pulsed macrophages (MO) were cultured for 1 week to yield a population enriched in antigen-specific (selected) T cells. These cells bind specifically within hours to fresh autologous antigen-pulsed MO. Thd dissociation of these selected PEL from antigen-pulsed MO was studied. No evidence was obtained that factors in the culture medium play a role in dissociation. Lymphocytes that have dissociated from antigen-pulsed MO are usually fully capable of rebinding to MO freshly pulsed with antigen, suggesting that there is no deficiency in the lymphocytes ability to bind. In contrast, readding antigen to cultures during incubation prevents the predicted dissociation. Moreover, repulsing MO cultured without selected PEL restores their capacity to bind fresh selected PEL. These findings indicate that decay of antigen associated with with MO is the major mechanism underlying the observed dissociation.

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PubMed1977

Specific binding of T lymphocytes to macrophages. I. Kinetics of binding.

Peritoneal exudate lymphocytes obtained from immune guinea pigs and cultured for 1 week on antigen-pulsed autologous macrophages were tested for their ability to bind to fresh antigen-pulsed autologous macrophages or to macrophages pulsed with an irrelevant antigen. Up to 30% of the lymphocytes bound to macrophages bearing the relevant antigen whereas only 2 to 5% remained nonspecifically bound to macrophages after vigorous washing. Specific binding was observed in cultures as early as 1 hr. Analysis of the kinetics of binding suggests that the observed nonspecific binding is not a step in specific binding. The possibility that weaker antigen-independent association between lymphocytes and macrophages precedes specific binding cannot be excluded. No evidence was obtained that serum antibody adsorbed to the macrophage or T cell plays a role in this cell interaction or that the T cell can bind antigen directly. We suggest that the observed specific binding represents the initial event in stimulation of T lymphocytes by antigen.

Animals↗
PubMed1977

Specific binding of T lymphocytes to macrophages. II. Role of macrophage-associated antigen.

Peritoneal exudate lymphocytes from immune guinea pigs that bind in vitro to autologous antigen-pulsed macrophages were allowed to proliferate for 1 week to give a population markedly enriched in antigen-specific T cells. This enriched population was then studied with regard to its binding to fresh autologous antigen-pulsed macrophages. Specific binding was not inhibited by a large excess of antigen in the media (5000-fold greater than the amount of antigen associated with the macrophages) either soluble or bound to Sepharose beads, or by coating the antigen-pulsed macrophags with antibody to the exogenous antigen, by reacting a second layer of antibody to the heterologous antibody, or by haptenating the antigen and treating the hapten-antigen macrophage complex with excess anti-hapten antibody. Results of treating antigen-pulsed macrophages with the proteolytic enzymes trypsin and pronase indicate that exogenous antigen is on the macrophage surface, but the experiments failed to prove that the removable antigen is essential for binding. The simplest interpretation of these results is that the T cell receptor is not specific for native exogenous antigen.

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PubMed1975

Cell surface immunoglobulin. XII. Localization of immunoglobulin on murine lymphocytes by scanning immunoelectromicroscopy.

The localization of immunoglobulin (Ig) on the surface of murine splenic lymphocytes has been studied with the scanning electron microscope (SEM), using a rabbit F(ab')2 hybrid antibody directed against mouse Ig and tobacco mosaic virus (TMV) with TMV as a morphological marker. 35% of spleen cells and 3% of thymus cells were labeled by this method. Labeled cells were usually small lymphocytes with moderate numbers of microvilli. The Ig molecules were randomly distributed on the lymphocyte surface, appearing on microvilli as well as on the smooth surface of the cell.

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PubMedDate not supplied

A role for TGF-beta in the suppression by murine bronchoalveolar cells of lung dendritic cell initiated immune responses.

Effective pulmonary immune responses likely require both local antigen presenting cells (APC) and regulatory suppressor cells. Bronchoalveolar cells (BAC), which consist primarily of alveolar macrophages (AM), are poor APC in most species and are often suppressive. However, dendritic cell (DC)-enriched populations from both lung interstitium and BAC have potent APC activity as measured by their capacity to stimulate both alloantigen and antigen-induced lymphoproliferative T cell responses. To determine if BAC could down-regulate pulmonary immune responses, BAC were mixed with DC-enriched loosely adherent lung interstitial cells (LAd) in a mixed leukocyte reaction (MLR). With high numbers of BAC, MLRs were consistently suppressed and suppression was partially reversed by the addition of indomethacin and catalase. Supernatants from BAC cultured with either syngeneic or allogeneic T lymphocytes in the presence of indomethacin and catalase markedly suppressed an MLR, while supernatants from BAC cultured alone were inconsistently suppressive. Antibodies to TGF-beta completely reversed the BAC-T cell supernatant-induced suppression of the MLR. However, TGF-beta antibody only partially reversed BAC-induced suppression when BAC were added directly to MLR cultures that contained indomethacin and catalase, suggesting that, in addition to TGF-beta, prostaglandins, and H2O2, BAC in culture with LAd and allogeneic T cells also produced short-lived suppressive factors and/or mediated suppression by direct cell contact. Thus, resident BAC likely utilize multiple mechanisms including TGF-beta secretion to suppress intra-alveolar immune responses initiated by lung DC.

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