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Biomedical subjects

W L Ford

Publications and source records attributed to W L Ford.

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

Lymphocyte traffic in pregnant or oestrogen stimulated rats.

Lymphocyte migration was studied at three stages of rat pregnancy by the tracer sample principle of injecting syngeneic thoracic duct lymphocytes labelled with chromium-51 (for organ counting) or [3H]leucine (for autoradiography). Except for one abnormal embryo no entry of lymphocytes into the foetus was detected. There was a small localization of lymphocytes in the placenta which did not differ significantly between allogeneic or syngeneic mating. Pregnancy produced little or no alteration of lymphocyte traffic into the spleen or lymph nodes, including those draining the uterus. The administration of oestrogens to virgin rats increased the height of the specialized endothelium lining the post-capillary venules in the mesenteric lymph nodes but had no effect on lymphocyte traffic.

Animals↗
PubMed1984

Afferent lymph and lymph borne cells: their influence on lymph node function.

In AO rats the afferent lymphatics to the right cervical lymph nodes (LN) were interrupted and the LN were encased in silicone rubber tubes to prevent reunion of the lymphatics. At regular intervals over the next 12 weeks the following were measured in comparison with the intact contralateral LN - LN weight, influx of lymphocytes from the blood, blood flow, the incorporation of 125IUdR and the incorporation of 35S-sulphate into high endothelial venules (HEV). Systematic histological observations are also reported. One day after deafferentization lymphocyte influx was significantly reduced although blood flow was unchanged and a temporary increase in LN weight was associated with crowding of the lymphatic sinuses with small lymphocytes. The subsequent decline in lymphocyte influx was biphasic and quicker than the decline of other parameters--being undetectable by 6 weeks. Flattening of HEV and diminished secretion of 35S-sulphate was noted at 1 week and progressive degeneration and eventual disappearance of the HEV network was seen by 6-12 weeks. Doubtlessly because of lack of antigenic stimulation 125IUdR incorporation, and numbers of lymphoblasts, plasma cells and finally germinal centres were progressively reduced. The numbers of macrophages and interdigitating cells (IDC) were greatly reduced by 3 weeks and very few were present at 6 weeks probably because most or all arrive in afferent lymph and have a limited life span in the LN. At 12 weeks the LN was difficult to recognize as such since only stromal cells and occasional small lymphocytes remained. In supplementary experiments u.v. irradiation of the LN at the time of deafferentization reduced lymphocyte influx without affecting blood flow suggesting that a u.v. sensitive cell like the IDC may influence lymphocyte influx. In conclusion the involution of the deafferentized LN is partly due to the lack of antigen but progression to the complete loss of specialized structure and function is probably due to lack of other factors including non-lymphoid cells that normally arrive in afferent lymph.

Animals↗
PubMed1984

The significance of changes in blood lymphocyte populations following surgical operations.

After surgery blood lymphocyte levels fell to one-third of the pre-operative value. Since this depression was transient, and followed the peak of serum cortisol closely, it was probably due to a redistribution of lymphocytes from the blood to the tissues. The proportion of activated lymphocytes, as measured by the incorporation of 3H-thymidine in vitro without added mitogen, was substantially increased about 5-8 days after operation. The greatest number of S-phase lymphocytes was found after operation combined with blood transfusion but surgery alone and blood transfusion alone each produced significant increases. The proportions of B lymphocytes, T helper cells and T suppressor cells remained nearly constant despite the fluctuations in total lymphocyte counts. The response of lymphocytes in vitro to phytohaemagglutin (PHA) was doubled on average 7 days after surgery provided the test was performed in the patient's own serum. In pooled serum there was no consistent change in the response to PHA. It is argued that none of the observed changes necessarily signify that a phase of immunosuppression follows surgical operations.

Blood Transfusion↗
PubMed1983

The migration of lymphocytes across specialized vascular endothelium. VI. The migratory behaviour of thoracic duct lymphocytes retransferred from the lymph nodes, spleen, blood, or lymph of a primary recipient.

Thoracic duct lymphocytes labelled with 51Cr were injected into a primary recipient and then were transferred for a second time from the lymph nodes (cervical and/or mesenteric), spleen, lymph, or blood into a series of final recipients. Measurement of the organ distribution of labelled lymphocytes in the final recipients enabled three main conclusions to be drawn. (1) Lymphocytes that had localized in the spleen, mesenteric lymph nodes (LN), or cervical LN of the first recipient showed no tendency to return in increased numbers to the same organ in the final recipient. (2) Lymphocytes that had recently entered the spleen or LN were temporarily impaired in their ability to reenter LN. This capacity was recharged when the cells returned to the lymph and the blood. (3) Lymphocytes that had been passaged from blood to lymph and collected for up to 4 hr at room temperature entered the LN of a recipient much faster than did nonpassaged thoracic duct lymphocytes collected overnight at 0 degree C. Supplementary experiments indicated that the different migratory behavior of thoracic duct lymphocytes under these two circumstances was mainly a consequence of their handling in vitro during the collecting and the labelling procedures. This functional impairment was not associated with a diminished ability to enter the spleen and bone marrow or to survive in recipients for up to 24 hr.

Animals↗
PubMed1983

The migration of lymphocytes across specialized vascular endothelium VII. The migration of T and B lymphocytes from the blood of the athymic, nude rat.

The primary migration of lymphocytes from the blood was compared in nude rats and in euthymic rats. The flatter endothelium in the post-capillary venules (PCV) in the lymph nodes of nude rats was as efficient as the high endothelium of PCV in euthymic rats at capturing both T and B lymphocytes from the blood, although lymphocytes took a longer time to cross the PCV wall in nude recipients. The organ distribution of both lymphocytes and lymphoblasts ([125I]UdR-labelled cells) was broadly similar in nude and euthymic recipients. A second aim was to compare B and T lymphocytes with respect to the rate and sites at which they leave the blood after intravenous injection. As judged by sampling venous blood, B lymphocytes left the blood faster, but this was partly attributable to a larger intravascular pool of B lymphocytes in small blood vessels, especially in the lung. Thoracic duct lymphocytes from nude rats collected under standard conditions (16 h, O degrees C) entered the cervical lymph nodes very poorly, but when lymphocyte transfer was performed under more physiological conditions entry of B lymphocytes into lymph nodes was about half that of T lymphocytes. B lymphocytes did show a slight preference for entry into Peyer's patches compared with lymph nodes.

Animals↗
PubMed1983

The recirculation of T and B lymphocytes in the athymic, nude rat.

The recirculation of lymphocytes through the tissues and their return to the blood were compared in nude and euthymic rats. Three approaches were used: the organ distribution of 15Cr-labelled lymphocytes from nude or euthymic donors at 24 h after injection; the compartmental distribution of B and T lymphocytes as assessed by autoradiography of the spleen, lymph nodes, and Peyer's patches; and the tempo of recirculation from blood to thoracic duct lymph as estimated by counting timed fractions of lymph from a recipient of labelled lymphocytes. The following conclusions were drawn: (1) The distribution of lymphocytes between organs and within organs is very similar in nude and euthymic recipients. In particular, B lymphocytes proceed normally to the follicular areas in the absence of T cells. (2) The recirculation from blood to lymph is delayed in nude rats. (3) For equal numbers of B and T cells injected intravenously about half as many B cells as T cells enter mesenteric and cervical lymph nodes, but approximately equal numbers of B and T cells enter the spleen and Peyer's patches.

Animals↗
PubMed1983

The rapid elimination of allogeneic lymphocytes: relationship to established mechanisms of immunity and to lymphocyte traffic.

Allogeneic lymphocyte cytotoxicity (ALC) refers to the destruction of lymphocyte beginning within a few hours of intravenous injection into non-sensitized, allogeneic recipients. Usually this has been detected in rats and mice by comparing the localization of 51Cr-labelled lymphocytes in the tissues of allogeneic and syngeneic recipients. In a particular strain combination the existence of ALC is supported by deficient localization of allogeneic lymphocytes in the LN, lungs and blood mononuclear population and an excess of the label that had been associated with allogeneic cells in the lymph plasma, blood plasma and kidneys. As the destruction of the allogeneic cells occurs in the lymphatic tissues, especially the spleen, it is paradoxical that there is sometimes an excess of the label associated with allogeneic cells in the spleen but evidence is presented that most of the isotope is no longer associated with living cells in that organ at 24 h after transfer. The data cannot be explained by an altered distribution of allogeneic lymphocytes between different organs. Experiments on the early migration of lymphocytes from the blood of syngeneic and allogeneic recipients point unequivocally to the conclusion that the adhesion of lymphocytes to specialized vascular endothelium in LN and their consequent entry into LN does not require that the lymphocytes and the endothelial cells share MHC products. The characteristics of ALC stressed in this review include the following: 1) it is independent of T-cell activation, either of host T-cells or of donor T-cells: 2) B- and T-cells are about equally vulnerable to ALC; 3) it varies greatly between different strain combinations regardless of other indices of cellular and humoral immunity; 4) F1 hybrid donor cells are vulnerable but the effect is always less marked than with allogeneic cells; 5) ALC is less radio-sensitive than primary cellular or humoral immune responses; 6) adoptive transfer of ALC can be achieved with TDL from nude rats. The possible mechanism underlying ALC has been debated in terms of natural killer cells recognizing certain allo-antigens or alternatively pre-existing "natural" antibody with low affinity for allogeneic cells leading to their elimination by ADCC. The argument hinges on the necessity for antibody and cannot be resolved by current data.

Animals↗
PubMed1983

The recirculating lymphocyte pool of the rat: a systematic description of the migratory behaviour of recirculating lymphocytes.

A comprehensive study of lymphocyte traffic in AO rats was performed under conditions as near to the physiological state as was practicable. In the light of previous results on the effect of environmental factors on the migratory behaviour of lymphocytes, thoracic duct cells were passed from blood to lymph in an intermediate rat before injection into a series of recipients for examination at time intervals from 1 min to 24 hr. At 1, 2 and 5 min after injection most of the labelled cells were in the blood, lungs and liver. The concentrations in these compartments fell over the next 25 min as the cells entered the spleen, lymph nodes (LN) and Peyer's patches according to a regular pattern. The peak localization in these latter organs occurred between 1 hr and 18 hr. Each organ had a characteristic time pattern of lymphocyte localization. Entry into mesenteric LN lagged behind other LN until 2.5 hr after injection following which mesenteric LN localization easily outstripped that in other LN to reach a delayed peak at 18 hr. Intravenously injected lymphocytes began to reappear in thoracic duct lymph in large numbers earlier than in previous studies so that the time taken for most T lymphocytes to cross LN from blood to lymph fell within the broad time band of 4-18 hr. Lymphocytes took on average 5-10 min to cross high endothelial venules when entering LN from the blood.

Animals↗
PubMed1982

Migration of lymphocytes across specialized vascular endothelium. V. Production of a sulphated macromolecule by high endothelial cells in lymph nodes.

High endothelial cells lining the post capillary venules in the paracortical areas of rat lymph nodes were found by autoradiography to incorporate [35S]sulphate, whether it was injected into the footpad to reach the draining popliteal lymph node or added to short-term cultures of cervical lymph node slices. The early localization of [35S]sulphate was confined to the Golgi apparatus, but before it disappeared from the cell radioactivity was associated with cytoplasmic vesicles. Sulphated material in macromolecular form was extracted from lymph nodes that had been labelled in vivo and was also found in the supernatant of lymph node cultures. The labelled material was not proteoglycan in nature. High endothelial cells apparently secrete a sulphated macromolecule but its relationship to the only known function of high-walled endothelium--the selective extraction of lymphocytes from the blood--remains to be clarified.

Animals↗
PubMed1981

Factors influencing the fate of 111indium-labelled lymphocytes after transfer to syngeneic rats.

Thoracic duct lymphocytes were labelled in vitro with 111indium-oxine or 111indium-acetylacetone in order to follow their migration after i.v. injection into syngeneic rats. Under certain conditions both preparations produced results with quantitatively confirmed data obtained by other approaches to the physiological pattern of lymphocyte recirculation. However, three significant difficulties were identified: (1) chemical toxicity by minor contaminants of the preparation; (2) radiation damage indicated by a progressive impairment of the recovery of radioactivity from lymph nodes. A labelling concentration of 20 microCi/10(8) cells was the highest compatible with survival of most lymphocytes for 24 h in vivo as confirmed by autoradiography; (3) rapid loss of 111In in vivo found at labelling concentrations below 1 microCi/10(8) cells. By one week after the injection of lymphocytes labelled at 20 Micro/Ci/10(8) cells most of the 111In had been transferred from lymphocytes to non-recirculating radioresistant cells within the spleen and lymph nodes.

Animals↗
PubMed1981

The stimulus to host cell proliferation in graft-versus-host reactions.

Two experiments are described concerned with the mechanism of host cell activation in the rat popliteal lymph node (LN) undergoing a graft-versus-host (GVH) reaction. (1) Irradiated, F1 hybrid hosts (750 rad) mounted an impaired response to parental strain T cells. This was augmented by an intravenous injection of F1 hybrid lymphocytes but not by parental strain B lymphocytes syngeneic with the initiating T cells. When the donor T cells (footpad) and B lymphocytes (intravenous) were completely allogeneic the residual response of the irradiated F1 was completely inhibited. (2) The popliteal LN response in the semi-allogeneic situation of the type (A x C)F1 leads to (B x C)F1 was, if anything, weaker than in the allogeneic situation AA leads to BB. These results and other data are discussed in terms of a possible major histocompatibility complex (MHC) requirement for host cell activation. The sharing of an MHC haplotype between donor and host cells is unlikely to be a necessary or sufficient condition for host cell activation.

Animals↗
PubMed1981

The sequence of changes in blood flow and lymphocyte influx to stimulated rat lymph nodes.

The rat popliteal lymph node was studied from 1 hr to 8 days after the footpad injection of either sheep erythrocytes or syngeneic rat erythrocytes. The following were measured relative to the contralateral (unstimulated) lymph node: (i) blood flow; (ii) lymph node weight; (iii) influx of lymphocytes from the blood; (iv) [3H]-thymidine incorporation; (v) [35S]-sulphate incorporation into macromolecular form (chiefly by high endothelial venules). After the arrival of sheep erythrocytes all five quantities showed substantial increases which began in a definite sequence. The blood flow started to rise first and may have been the main factor contributing to the later increase in lymphocyte influx. Increased sulphate incorporation began later than the rise in lymphocyte influx. After the injection of rat erythrocytes a small increase in lymphocyte influx was found without a corresponding increase in blood flow. In rats irradiated before the footpad injections lymphocyte influx increased three-fold after sheep erythrocytes, rat erythrocytes or PBS, again without a corresponding increase in blood flow. Thus while variation in blood flow to high endothelial venules is one important factor in determining the supply of lymphocytes to the lymph node other factors are operative in certain situations.

Animals↗
PubMed1981

A method for following human lymphocyte traffic using indium-111 oxine labelling.

A method is described whereby large numbers of human lymphocytes are separated from peripheral blood and labelled in vitro with indium-111 oxine. Following autologous reinjection, the distribution within the body is followed by means of serial blood samples, surface-probe counting and gamma camera imaging. The distribution of radioactivity following reinjection of heat-damaged labelled lymphocytes and free indium-111 oxine is different from that of 'normal' lymphocytes. The results suggest that the separation and labelling procedure does not cause significant physical damage to the lymphocytes The importance of restricting the specific lymphocyte activity to 20-40 microCi per 10(8) cells in order to minimize radiation damage to the lymphocytes is emphasized. Good resolution of lymphoid structures is obtained using gamma camera imaging and the changes recorded in organ distribution correlate well with data from animal models of lymphocyte migration. Thus, indium-111 oxine labelling of human lymphocytes provides a non-invasive method whereby the migratory properties of human lymphocytes can be followed.

Cell Movement↗
PubMed1981

Human lymphocyte traffic assessed by indium-111 oxine labelling: clinical observations.

Clinical studies using indium-111 oxine labelling of human peripheral blood lymphocytes are presented. Data from animal models of lymphocyte migration are compared with results found in healthy subjects and patients with malignant neoplasms. The physiological significance of bone marrow and liver localization on gamma camera imaging is discussed and the importance of considering the surface marker characteristics of the lymphocytes under study, when interpreting results, is emphasized. The possibility that the redistribution of lymphocytes within the body is a cause of the peripheral blood lymphopenia in patients with Hodgkin's disease and other malignancies is suggested, and the usefulness of indium-111 oxine labelling in clarifying this problem is proposed.

Cell Movement↗