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W L Ford

Publications and source records attributed to W L Ford.

15 recordsLinked to original sources
PubMed1978

Selection of antigen-specific cells by adherence to allogeneic cell monolayers: cytolytic activity, graft-vs.-host activity and numbers of adherent and nonadherent cells.

Rat lymph node cells taken at the peak of cytolytic activity following a skin allograft were separated into adherent and nonadherent fractions by incubation on monolayers of thoracic duct lymphocytes either of the same strain as the graft donor or of an Ag-B different strain. In the face of a 3-fold enrichment of cytolytic activity in the adherent cells and a 3-fold depletion in the nonadherent cells there was no detectable partition of graft-vs-host (GVH) activity. Supplementary experiments supported the simplest interpretation of this finding, namely that the antigen receptors on GVH-reactive cells did not influence their adherence in this system. Similarly, there was no partition of the GVH activity of nonimmune lymph node cells by adherence. Labeling lymph node cells with either radioactive uridine or thymidine in vitro, suggested that about 20% of DNA-synthesizing cells in the immune population adhered because of antigen recognition.

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PubMed1978

Recirculation of lymphocytes: its role in implementing immune responses in the skin.

A number of recent investigations have suggested that the subset of lymphocytes which migrate into nonlymphoid tissue to appear in peripheral lymph may be partly different from the major recirculating pool migrating through lymphoid tissues. We report results on the migrating from the blood of thoracic duct lymphocytes labelled with Cr and three subsets-accredited recirculators, activated lymphocytes and long-lived lymphocytes. The localization of these populations was studied in normal skin, in a contact sensitivity lesion and in a site of non-immune inflammation. All four populations localized in the contact sensitivity lesion in increased numbers compared to normal skin but long-lived lymphocytes appeared to discriminate between cell-mediated immunity and non-immune inflammation; activated lymphocytes migrated most efficiently into the non-immune inflammatory site (Table 4).

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PubMed1977

A comparison of immune responses against AG-B and non-AG-B antigens, presented alone or together.

By exploiting congenic rat strains (HO.B2 and PVG/c) cell-mediated immune responses against Ag-B antigens alone were measured and compared with responses against (1) non-Ag-B antigens and (2) Ag-B and non-Ag-B antigens in combination. It was confirmed that multiple non-Ag-B antigens provoke prompt first-set skin graft rejections, but are much weaker than Ag-B antigens in stimulating both graft-versus-host (GVH) and cytotoxic activity. No evidence of synergistic interaction was found between anti-Ag-B and anti-non-Ag-B responses either by GVH assay or in the generation of cytotoxic cells. Specific partitioning of cytotoxic cells on antigenic monolayers suggested that cytotoxic cells on antigenic monolayers suggested that cytotoxicity is predominantly directed against Ag-B antigens. The measurements of GVH activity consolidate previous work, which suggested that 4.5 to 12% of nonimmune T cells can respond to each Ag-B determined antigenic complex and eliminate the possibility that most of these cells were responding to non-Ag-B antigens. Two principles for measuring GVH activity were compared: (1) 3H-thymidine incorporation into donor lymphocytes at 24 hr after transfer to irradiated F1 hybrid recipients and (2) the popliteal lymph node assay, which depends on a secondary phase of host cell proliferation.

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PubMed1977

The migration of lymphocytes across specialized vascular endothelium. III. Concanavalin A delays lymphocytes in normal traffic areas.

Radioactively labelled rat lymphocytes were treated in vitro with concanavalin A (con A) and injected intravenously into syngeneic recipients. By examining the blood and tissues at intervals from 30 min to 48 h after injection, it was confirmed that con A altered the distribution of lymphocytes. Comparison was made with the localization of alternatively labelled untreated lymphocytes injected into the same recipients and with untreated lymphocytes injected into other recipients. Within 1 h of injection there was a surplus of treated cells in the lungs and liver and deficits (of equal magnitude) in the blood, spleen and lymphonodes. By 24 h after injection there was a twofold surplus of treated cells in the spleen but a persisting deficit in lymphnodes. These perturbations can be ascribed to the prolonged retention of lymphocytes in normal sites of localization; there is no evidence that con A either hinders the migration of lymphocytes from the blood or diverts them to abnormal sites. It is not clear whether the delay in the recipients' tissues requires an active response to con A but, if so, then it does not proceed to blastic transformation.

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PubMed1977

An experimental comparison of radioactive labels with potential application to lymphocyte migration studies in patients.

The suitability of two radionuclides (99mTc, 111In) for labelling lymphocytes have been evaluated in rats by comparison with a standard method using 51Cr. For the study of lymphocyte migration in patients labelling with 111In-labelled oxine is clearly the most promising because both in vivo and in vitro it remains associated with lymphocytes and the labelled cells migrate normally into lymphoid tissues. The physical characteristics of 111In are also favourable. Not only does 99mTc rapidly dissociate from lymphocytes but also it compromises their ability to recirculate from blood to lymph.

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PubMed1976

The migration of lymphocytes across vascular endothelium.

According to Morris and his colleagues the migration of lymphocytes from the blood into inflammatory sites is a morphologically similar process to the large scale migration of lymphocytes into the paracortex of lymph-nodes which occurs under normal conditions. Little is known of the nature of the selective interaction between lymphocytes and specialized endothelial cells although several investigators have tested the migratory properties of lymphocytes which have been treated in vitro with enzymes or lectins and injected i.v. Such results are difficult to interpret because decreased lymph-node localization may be secondary to increased localization elsewhere. To overcome these difficulties the mesenteric lymph-node chain of the rat was perfused at 37 degrees C for 30-60 minutes with rat serum at 0.33 ml/min. When labelled lymphocytes were added to the perfusate the uptake of cells into the lymph-nodes was 2.13 +/- 0.63% of the number of which had passed through the preparation and this fraction was independent of the concentration in the perfusate over a wide range. No release of lymphocytes from the isolated node into the perfusate could be detected. Neuraminidase treated lymphocytes localized in the perfused lymph-node at least as well as did untreated lymphocytes in contrast to their deficient lymph-node localization following i.v. injection into intact recipients as originally found by Gesner. Other evidence has been found that the primary effect of neuraminidase treatment is to increase hepatic localization. Large lymphocytes migrate into the isolated node more readily than do small lymphocytes which is also in contrast to results in intact recipients. The migration of lymphocytes treated with trypsin or concanavalin A has also been studied.

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PubMed1975

Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes.

A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a "third party" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex.

Animals↗
PubMed1975

Early cellular events in a systemic graft-vs.-host reaction. II. Autoradiographic estimates of the frequency of donor lymphocytes which respond to each Ag-B-determined antigenic complex.

A graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain (AO) lymphocytes into irradiated (AO times HO)F1 or (AO times DA)F1 hybrids. The proportion of donor T cells which had responded to the F1 hybrid antigens within 24 h was estimated by two methods. (a) Donor lymphocytes were labeled with [3H]uridine in vitro before injection. The proportion of labeled cells which had morphologically transformed in the recipient's spleen was 17-19%. In both series of experiments syngeneic transfers were performed in which case the proportion of transformed cells was 1-2.4%. A similar low proportion was found after parental to F1 transfer in a non-Ag-B strain combination. These figures were used to calculate the frequency of responding cells in the injected population given three additional pieces of information: (a) the extent of selection in the spleen which transformed the estimate to 4.5%-6.0% responders; (b) division of donor cells was shown to be negligible under the conditions of the experiment; and (c) the nonspecific recruitment of lymphocytes was shown to be negligible. A speculative model of antigen recognition by T cells which accounts for the high proportion of responders is outlined.

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