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Biomedical subjects

W L Ford

Publications and source records attributed to W L Ford.

At least 55 records · Page 3Linked to original sources
PubMed1980

The selective adherence of lymphoblasts to antigenic cell monolayers. A method for determining the specificity of lymphocytes proliferating in response to histocompatibility antigens.

The specificity and intensity of the immune response of rat lymph nodes draining a skin allograft were examined by exploiting a monolayer of donor-type thoracic duct lymphocytes as an immunoabsorbent. Stable monolayers were produced by attaching lymphocytes from different strains of rat to Petri dishes pretreated with poly-L-lysine. The responding lymph node cells were labelled in vitro with [3H]Thymidine, incubated on the monolayer and mechanically separated into non-adherent and adherent fractions. The radioactivity associated with the adherent fraction was 7--8 times greater when the monolayer displayed the immunizing major histocompatibility antigens than when syngeneic or 'third party' monolayers were used. The non-specific adherence to syngeneic monolayers was low and consistent. Immunization to minor histocompatibility antigens may also be studied by this method.

Adsorption↗
PubMed1980

The architecture of rat lymph nodes. III. The lymph nodes and lymph-borne cells of the congenitally athymic nude rat (rnu).

The lymph nodes (LN) of the congenitally athymic nude rat(rnu) were compared with the LN of non-nude littermates. The mesenteric and coeliac LN were smaller in the rnu rats, but the axillary and the cervical LN were larger. Germinal centres were found in the LN of nude rats. They were scarce and often very small, but some were of normal structure, especially in the cervical LN. The endothelium of post-capillary venules in the LN or normal rats, was seen. The paracortex was extremely depleted of lymphocytes but remained a distinct area occupied predominantly by pale interdigitating cells. In some LN the medullary sinuses were distended and the cords engorged with plasma cells. The predominant cells in thoracic duct lymph were immunoglobulin-positive B lymphocytes. The hourly output of these cells was the same as that in non-nude littermates. However, small numbers of thoracic duct cells were positive for the markers identified by the monoclonal antibodies W3/13 and W3/25, although in normal rats these are not expressed on small B lymphocytes.

Animals↗
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.

Animals↗
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).

Animals↗
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.

Animals↗
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.

Animals↗
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.

Animals↗
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.

Animals↗
PubMed1976

The migration of lymphocytes across specialized vascular endothelium. I. The entry of lymphocytes into the isolated mesenteric lymph-node of the rat.

The chain of lymph-nodes in the rat mesentery was isolated and the preparation was perfused via cannulae in the superior mesenteric vessels. The perfusate consisted of serum to which labelled lymphocytes had usually been added. The entry of radioactively labelled lymphocytes from the blood vessels into the lymph-nodes was studied by scintillation counting and autoradiography. It was observed that: (1) In the perfused node labelled lymphocytes localized in and around post-capillary venules in the paracortex as they do early after i.v. injection. (2) The number of lymphocytes which entered the node was directly proportional to the concentration in the perfusate over the range studied. The proportion of cells retained in the node varied considerably around a mean of 11% of lymphocytes reaching it. (3) The isolated lymph-node released few if any lymphocytes into the effluent (venous) perfusate. (4) Large lymphocytes migrated into isolated lymph-nodes slightly more readliy than did small lymphocytes. (5) Unlike intact cells isolated lymphocyte membranes did not adhere to specialized vascular endothelium.

Animals↗
PubMed1976

The migration of lymphocytes across specialized vascular endothelium. II. The contrasting consequences of treating lymphocytes with tryspin or neuraminidase.

Lymphocytes were exposed in vitro to either trypsin or neuraminidase. The ability of the treated cells to migrate into tissues were measured (a) by i.v. injection into intact recipients and (b) by vascular perfusion through an isolated lymph-node preparation. The localization of trypsinized cells in the lymph-nodes of recipients was deficient when compared to untreated lymphocytes and there was a surplus of trypsinized cells in blood. Trypsinized cells migrated into the isolated nodes in reduced numbers. By contrast, neuraminidase treated lymphocytes were markedly deficient in the blood of recipients early after injection; their localization in the spleen and lymph-nodes was also deficient but they were in surplus in the liver. Moreover they migrated into the isolated nodes in slightly increased numbers. By 24 hr after injection the perturbed localization pattern produced by either enzyme was partly restored to normal. In conclusion, tryspin interfered with the capacity of lymphocytes to migrate into lymph-nodes but neuraminidase did not; the latter promoted the hepatic sequestration of cells and the reduced localization in the blood and tissues was a consequence of this. The hypothesis that lymphocytes adhere to specialized endothelia in lymph-nodes because of specific glycoside sequences on their surface lacks experimental support.

Animals↗