Severe Depletion Of Lymphocytes Research Articles

The isolation of Mycoplasm hyosynoviae and exposure of pigs to experimental infection.

Arginine-utilising mycoplasmas isolated from the pneumonic lungs of 4 pigs were identified as M. hyosynoviae by their growth characteristics, biochemical activity and serological similarity to each other and to 2 type strains of M. hyosynoviae in growth inhibition tests. A purified culture of one M. hyosynoviae isolate was inoculated intravenously into 3 pigs which were killed 9 days later. Although arthritis was not observed clinically, M. hyosynoviae was isolated from 8 of 9 joints cultured, the tonsils and retropharyngeal lymph nodes of all 3 pigs and the lungs of 2 pigs. No histopathological changes were observed in synovial membranes of the joints cultured or lungs but severe depletion of lymphocytes in the cortex of lymphoid follicles in lymph nodes and tonsils was observed.

Post-capillary venules as the pathway for migrating B lymphocytes.

Histological observation on the mesenteric lymph node and Peyer's patches of C3H B mice, neonatally thymectomized, lethally irradiated and reconstituted with syngeneic bone marrow cells, showed that a large number of lymphocytes appeared selectively in the restricted territory surrounding the post-capillary venules. Severe depletion of lymphocytes persisted in most of the thymus-dependent areas. Lymphocytes were also observed passing through the walls of the post-capillary venules. Autoradiographic studies on the mesenteric lymph node of recipient B mice 30 minutes after intravenous injection of cells labelled with 3H-uridine and taken from lymph nodes of donor B mice showed that B lymphocytes could penetrate the walls of the post-capillary venules from the blood into the peripheral lymphoid tissues. The post-capillary venules, which are known as the recirculating route of T lymphocytes in normal animals, are thought to be the pathway of migrating B lymphocytes in B mice.

Suppression of cellular immunity in rats and mice by maternal treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Treatment of female F-344 rats and C57B1/6 mice with 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) during the latter half of gestation and in the postnatal period resulted in a severe depletion of lymphocytes in the thymic cortex of the offspring. Cellular immunity was impaired in these animals. Allograft rejection times were prolonged in rats and mice. Graft-versus-host (GVH) activity of spleen cells as well as the response of rat thymus and spleen cells to phytohemagglutinin (PHA) was reduced on a cell-for-cell basis. No reduction occurred in the response of thymus cells to concanavalin A (Con A). Maternal treatment postnatally on day 0, 7 and 14 with 5 <i>μ</i>g TCDD/kg of body weight reduced total PHA and Con A response recoverable from the thymus by 91 and 74%, respectively. Histologically, depletion of thymic cortex was not due to lymphocyte destruction. There was no adrenal hypertrophy. Stress-induced release of glucocorticoids is not considered responsible for the immune suppression observed. In contrast to the marked effects in early life, reduced responsiveness of spleen cells to PHA in mice treated with TCDD when 1 month old was only seen at a dose level that was clearly toxic. In 4-month-old mice, PHA responsiveness as well as GVH activity were not decreased. Response of unstimulated and stimulated thymus and spleen cell cultures was not reduced by adding TCDD <i>in vitro</i>. In TCDD-exposed rats, decreased eosinophilia was observed in acidophilic cells in the adenohypophysis. This finding is discussed in view of the effect of TCDD on the thymus, and a possible mode of action of TCDD is proposed.

The growth of tumours in T-cell deprived mice and their response to treatment with Corynebacterium parvum.

Severe depletion of thymus-derived lymphocytes does not reduce, and may significantly increase, the resistance of mice to syngeneic tumours, although it grossly impairs their ability to reject allotransplants. Injection of killedC. parvumcauses further inhibition of tumour growth in T-cell deprived mice to an extent comparable to that resulting from the same dose ofC.parvumin normal mice. This appears to lend support to the hypothesis that the antitumour effect ofC. parvumdepends primarily on macrophage stimulation.

Mechanisms of leukocyte production and release. XI. Appearance of leukocytosis-induced factors following treatment with anti-lymphocyte serum.

Abstract The present experiments were undertaken to determine the possible existence of a lymphocytosis-promoting factor in the plasmas of rats in which severe lymphocyte depletion was induced by the administration of rabbit, anti-rat lymphocyte sera (RARLS). Initial attempts to demonstrate the presence of such a factor were inconclusive. However, the possible presence of residual RARLS in the pooled donor plasmas necessitated the additional step of incubating the plasma with goat, anti-rabbit gamma globulin (GARGG) to remove the residual antiserum activity. Injections of this plasma into normal rats resulted in highly significant increases in their peripheral leukocyte numbers. This suggests that the depression of the leukocyte numbers produced by RARLS in the donor animals evoked the production of leukocytosis-inducing factors.

Virus-induced alterations of lymphoid tissues: I. Modification of the recirculating pool of small lymphocytes by Newcastle disease virus

Intravenous inoculation of Newcastle disease virus (NDV) altered the character of the recirculating pool of small lymphocytes. In mice severe lymphocytopenia and depletion of small lymphocytes from the deep cortex of lymph nodes and from the periarteriolar lymphoid sheaths of the spleen were found 24 hr after virus challenge. By 72 hr the concentration of blood lymphocytes was normal and the areas in the lymph nodes and spleens which were depleted at the earlier interval showed an increased concentration of lymphocytes. In virus-treated rats it was also shown that depletion and repopulation of blood with lymphocytes were paralleled by similar changes in the output of small lymphocytes from the thoracic duct. Thus, a marked deficit of small lymphocytes in the thoracic duct lymph was observed when rats were cannulated at the time of virus challenge; the output of small lymphocytes in the lymph was normal when rats when cannulated 72 hr after virus inoculation. Evidence was obtained that the ability of NDV to modify the recirculating lymphocyte population was independent of its capacity for complete viral replication and independent of functioning adrenal gland tissue. Possible mechanisms that may account for these abrupt and marked shifts in the concentration of recirculating lymphocytes in the blood, lymph, and lymphoid tissues are discussed.

抗胸腺,抗ファブリシウス嚢リンパ球血清の免疫抑制効果に関する研究

Rabbit anti-thymic and anti-bursal lymphocyte sera (hereafter abbreviated to RATLS and RABLS, respectively) were examined for immunosuppressive effect on the hemolytic plaque-forming cells (PFC) and rosette-forming cells (RFC) in the spleen, and on experimental allergic encephalomyelitis (EAE) in chickens. The results obtained are as follows:1) RATLS anb RABLS had a high lymphoagglutinating activity on the thymic and bursal lymphocytes, respectively. In addition, a cross-reaction was observed between both anti-lymphocyte sera. This suggests that the thymic and bursal lymphocytes may have common antigen(s) in addition to the respective specific antigen(s) on the surface of the cell.2) Repeated administration of RATLS caused a more remarkable fall in lymphocyte count of the peripheral blood than that of RABLS. Furthermore, severe depletion of lymphocytes in the white pulp of the spleen was a characteristic change caused by RATLS, and a slight decrease in lymphocytes and pyroninophilic cells and the appearance of ill-defined germinal centers were ones induced by RABLS.3) In the primary response, when RABLS was injected daily for five days following the sensitization with sheep erythrocytes, there was a marked decrease in the number of PFC and RFC in the spleen. In contrast, such a suppression by RABLS was not so marked in the secondary response in previously immunized birds. On the other hand, RATLS was found to have a weak suppressive effect only in the primary response.4) The occurrence of EAE and the delayed-type hypersensitivity (wattle test) to the encephalitogenic basic protein of myelin were suppressed remarkably by the repeated injection of RATLS, but much less remarkably by the repeated administration of RABLS.From the findings obtained, it was ascertained that RATLS exerted a suppressive effect selectively on the cell-mediated immune reaction, and that RABLS did such an effect on the humoral antibody production. Therefore, both anti-lymphocyte sera were proved to have a considerably high selective activity in their immunosuppression.

The Effects of Extracorporeal Irradiation of Circulating Blood and Thoracic Duct Lymph on Tetanus Antitoxin Responses in Calves

Calves were given daily extracorporeal irradiation of circulating blood (ECIB), continuous extracorporeal irradiation of thoracic duct lymph (ECIL), and thoracic duct cell depletion by continuous centrifugation to determine the effects of lymphocyte depletion on primary and secondary antibody responses to tetanus toxoid. These procedures induced a severe depletion of small lymphocytes in circulating blood and thoracic duct lymph. Although the appearance of detectable serum antibody was delayed 5 to 10 days and peak titers were slightly reduced, all calves depleted of circulating lymphocytes gave nearly normal primary tetanus antitoxin responses. Repetitive ECIB to 250 to 860 blood volumes during a period of 10 to 30 days with accumulated radiation doses of 93,000 to 250,000 rads failed to significantly repress secondary responses to fluid tetanus toxoid. These findings are in sharp contrast to the well-known radio-sensitivity of antibody responses when total doses of 50 to 600 rads of ionizing radiation a...

Immunoglobulin Deficiencies in Thymic Alymphoplasia

In the article, "Selective Immunoglobulin Deficiency Associated with Thymic Alymphoplasia" (Pediatrics, 39:506, 1967), Drs. Buckley, Bradford, and Butcher state "the association . . . . lends further support to the hypothesis that immunoglobulin production can take place without a normal thymus and in the face of severe depletion of small lymphocytes." This interpretation by the authors of the findings presented agrees with that suggested in several previously described cases of similar nature. However, an alternative explanation has not been adequately considered in any of these published reports.

Effect of whole-body irradiation ad cortisone on the development of Ostertagia spp. in sheep.

In a sheep exposed to 300 rads only a slight reduction in antibody response was noted, although the leukocyte count dropped to a mininmum (48 hr post irradiation) of 960 per mm with only 2% lymphocytes in the differential count. In four sheep, which were irradiated with 440 rads, the hematological picture indicated a very severe depletion of body lymphocytes with total white cells dropping in all cases to less than 20% of the pre-irradiation figure. It was found that 440 rads whole-body irradiation will largely suppress the antibody response of sheep, but the sheep is likely to succumb to bacterial infection unless protected by antibiotics. In an attempt to determine whether the arrested development of parasite larvae is due to an immunological response by the host, an experiment was carried out with the object of destroying or reducing the host immunological response by the use of cortisone and whole-body irradiation. Larval arrest was found to be much less in cortisone treated (8.5%) and in the irradiated sheep (18.7%) than in the controls. It is postulated that in normal sheep which have had no contact with ostertagia spp or related parasites, a rapid, probably local, immunity reaction leads to themore » formation and release of factors causing a specific arresting of development of many of the parasites. (P.C.H.)« less