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J D Waterfield

Publications and source records attributed to J D Waterfield.

45 records · Page 3Linked to original sources
PubMed1977

Mechanism of action of suppressor cells. In vivo concanavalin-A-activated suppressor cells do not directly affect B cells.

The addition of a small proportion (10%) of in vivo concanavalin-A (Con-A)-activated spleen cells to normal spleen cell cultures suppressed the primary immune response to sheep erythrocytes (SRBC) but had no effect on the thymus-independent primary immune response to 3,5-dinitro-4-hydroxy-phenacetyl-conjugated lipopolysaccharide. When Con-A-activated cells were added after 24 h, there was no suppression of the anti-SRBC response but rather an enhanced response when few cells were admixed. Con-A-activated cells did not influence activation of normal cells by polyclonal T- and B-cell activators. It is concluded that Con-A-induced suppressor cells do not act on B cells but rather on helper cells (T cells or macrophages) at a very early stage of the immune response to thymus-dependent antigens.

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PubMed1977

Functional heterogeneity of splenic T lymphocyte subpopulations. I. Determination of splenic subpopulations by the use of mitogneic probes.

The results reported here suggest that there exist two T-cell-mitogenic responsive populations in the spleen--one that is responsive to concanavalin A (Con A) and a second one that is responsive to Con A and phytohemagglutinin (PHA). Using an in vitro restimulation system, we have found that a primary in vivo activation with Con A effectively suppresses the subsequent restimulation response to PHA. However, in the reverse experiment, a primary in vivo PHA activation had little effect on the ability of cells to be restimulated with Con A. The suppression seen was due to a refractory recovery period displayed by all cells after previous activation and not to a nonspecific steric hindrance of mitogenic activation receptors due to the lectin remaining on the cell surfaces.

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PubMed1976

The effect of membrane stabilizing agents on induction of the immune response. I. Effect of lymphocyte activation in mixed lymphocyte reactions.

The effect of three membrane-stabilizing agents, chlorpromazine, imipramine, and lidocain, on in vitro activation of cellular responses was studied using the one-way MLR. Cellular activation was found to be depressed by these drugs. However, the degree of suppression paralleled the decline of viable cells in the cultures. It is concluded that drug-induced inhibition of MLR was due solely to the toxicity of the compounds.

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PubMed1976

Lymphocyte-mediated cytotoxicity against tumor cells II. Characteristics and tissue distribution of concanavalin A-activated cytotoxic effector cells.

In vivo or in vitro activation of cytotoxic effector lymphocytes by concanavalin A (Con A) has been shown to result in a population of effector cells exhibiting a degree of immunological specificity when Con A was present during the cytotoxic assay (Waterfield, J.D. et al., Cell. Immunol. 1975. 17:392). In this communication we have characterized the Con A-activated effector cell by physical criteria and tried to assign it to a given subpopulation of thymus-derived lymphocytes. It was shown that macrophages played no role in target cell lysis in this system, nor was their presence required for Con A activation of the effector cell. The effector cell proved insensitive to anti-theta serum, but was classified as a T cell by the enrichment of cytotoxicity when a purified population of T cells was activated by Con A in vitro and by the failure to activate the effector cell in nude mice. Precursors of the effector cell were shown to reside primarily in the spleen, to be radioresistant up to 400 R, and to be short-lived after adult thymectomy. Thus, the effector cell can be classified with the T1 population of T cells and has similar characteristics as a cytolytically active cell described by Stobo et al. (J. Immunol. 1973. 110: 362, 652).

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PubMed1976

Lymphocyte-mediated cytotoxicity against tumor cells. III Differentiation of concanavalin A-activated cytotoxic effector cells.

The maturation of selected T cell responses in the lymphoid organs of irradiated CBA mice was followed after adoptive transfer of syngeneic fetal liver cells. Mitogenic responsiveness to phytohemagglutinin (PHA) and concanavalin A (Con A) was found to reach control values 3 weeks after reconstitution in the thymus, spleen, and lymph node, of fetal liver repopulated animals. Spleen and lymph node cell reactivity in mixed lymphocyte culture reactions required 6 weeks to reach significant values. However, the ability of spleen cell suspensions to be activated by Con A into cytotoxic effector lymphocytes appeared after only 2 to 3 weeks. It is concluded that two functionally distinct T cell subpopulations exist in the spleen, one which can be activated into cytotoxic effector lymphocytes by Con A, and one which responds to alloantigens by DNA synthesis.

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PubMed1976

Lymphocyte-mediated cytotoxicity against tumor cells specificity and characterization of concanavalin A-activated cytotoxic effector lymphocytes.

The selective T cell mitogen Con A was found to induce cytotoxic effectorlymphocytes after in vivo or in vitro treatment. The effector cells exhibited immunologic specificity when tested against tumor cells, killing targets only across H-2 histocompatibility barriers. Thus, Con A caused a polyclonal T cell activation, resulting in the appearance of effector cells capable of recognizing all H-2 antigens, except those coded for by the major histocompatibility loci of the lymphocyte donor. These experiments demonstrate that Con A is capable of activating pre-existing T cells to reveal their genetically determined immunological specificity, and furthermore suggest that there is a deletion of T cell clones with specificity for self. The activated effector cells were characterized as T blasts being relatively insensitive to treatment with anti-O serum plus complement. The precursors of the Con A-activated effector cells were shown to reside primarily in the spleen, to be radio-resistant up to 400 R, and to be short-lived after adult thymectomy. Thus, the population of T cells capable of activation to cytotoxic effector lymphocytes by Con A has similar physical characteristics to the splenic subset(s) of T cells mediating both GVH and cytotoxicity responses upon alloimmunization.

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PubMedDate not supplied

Tissue distribution and cytofluorometric analysis of oral mucosal T cells in the BALB/c mouse.

The incidence and distribution of Thy-1.2+, Lyt-2.2+ and L3T4+ cells in the murine oral mucosa were investigated using qualitative and quantitative approaches. From immunostaining of frozen tissue sections, it appeared that the majority of oral T cells are located either in the epithelium or within the minor salivary gland network. The occurrence of Thy-1.2+, L3T4+ and Lyt-2.2+ cells at these sites points to two strategic lines of defence in the event of mucosal infections or aggression. A quantitative analysis of oral T-cell subsets was made possible by optimizing an enzymatic digestion procedure which preserves all three T-cell surface markers. Flow cytometric analysis of oral mucosal cells demonstrated that the helper phenotype is about twice as numerous as the cytotoxic/suppressor phenotype in the mucosa. Furthermore, in single cell suspensions, virtually all Thy-1+ cells were either L3T4+ or Lyt-2.2+ in the mucosa and in the spleen. From this frequency analysis and our previous studies, we conclude that T cells are a major component of the oral immune system, being 2-3 times as numerous as B cells or macrophages. Present data on the spatial distribution and characteristic ratio of T-cell subsets assess the basal activity of the local T-cell populations in healthy animals and lay the basis for comparative studies of both qualitative and quantitative variations occurring during mucosal infections or autoimmune reactions.

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