Lymphocyte-mediated cytotoxicity: effects of ageing, adult thymectomy and thymic factor.

Adult thymectomy, as well as ageing, depressed splenic lymphocyte-mediated cytotoxicity (LMC) in the mouse. Ageing depressed significantly LMC as early as 19 weeks of age, independently of the number of cells used for immunization. Thymectomy affected LMC only when supoptimal numbers of immunizing allogeneic cells were used. This effect peaked at 6 to 12 weeks after thymectomy. No difference between thymectomized and normal mice was observed when LMC was tested 16 to 20 weeks after thymectomy, at an age when normal control mice themselves already showed a lowered LMC due to ageing. The effect of in vivo treatment with a circulating thymic factor (TF), which was shown to disappear with ageing as well as after adult thymectomy, has been tested in adult thymectomized mice and normal young and ageing mice. TF treatment prevented LMC depression in adult thymectomized mice, whereas it depressed paradoxically splenic LMC in normal young and old mice. The possible mechanisms of the effects of adult thymectomy, ageing, and thymic factor on the different T cell subsets involved in allogeneic killer cell generation are discussed.     

Anti-immunoglobulin stimulation of murine lymphocytes. III. Enhancement of the development of responsive B cells by thymic deprivation.

The development of splenic B cells that can be induced to proliferate by soluble anti-immunoglobulin (anti-Ig) reagents requires 7 to 9 months in normal mice. We have found that this age-associated response is enhanced by thymic deprivation. Both neonatally thymectomized LAF₁ mice and thymectomized, lethally irradiated, and bone marrow-restored Balb/c mice respond earlier and more strongly to anti-Ig than their sham controls. Nevertheless, at least 3–4 months are still required after thymectomy before a response can be measured. The earlier and enhanced response to anti-Ig seen in thymectomized animals is not due simply to an increase in the total number of Ig-positive spleen cells. The age-associated response of splenic B cells to anti-Ig we have observed in normal mice may be explained by the “natural” loss of thymic influence that occurs with age.     

Expression of insulin-like growth factor II (IGF-II) and histological changes in the thymus and spleen of transgenic mice overexpressing IGF-II

 Previously, transgenic mice were constructed overexpressing human insulin-like growth factor II (IGF-II) under control of the H₂k^b promoter. The IGF-II transgene was highly expressed in thymus and spleen, and these organs showed an increase in weight. In the current study we have analyzed the sites of IGF-II mRNA expression, the distribution of IGF-II, IGF-I, and both IGF receptors, and histomorphometrical changes in thymus and spleen. With in situ mRNA hybridization, expression of the IGF-II transgene is found with high intensity in the thymic medulla and in the white pulp/marginal zone of the spleen, whereas there were scattered positive cells in the thymic cortex and in the splenic red pulp. Hybridization was restricted to non-lymphocytic cells. Immunohistochemistry revealed intense IGF-II peptide staining with the same distribution as IGF-II mRNA. There was additional intense IGF-II staining of all elements in the splenic red pulp (including trabeculae) and diffuse, low level staining in the thymic cortex. These findings were not observed in control mice. In the thymic medulla, most IGF-II producing cells co-labelled with keratin, whereas a minor population also stained for the monocyte/macrophage marker MOMA-2. In the spleen, co-labelling of IGF-II producing cells was found with MOMA-1 (marginal zone), or with the dendritic cell marker NLDC-145 (red pulp). IGF-I and both IGF receptors were found in these organs in nearly all cell types, with a similar pattern in transgenic mice and in control animals. Histomorphometric analysis revealed a marked increase of thymus cortex size and an increased trabecular size in the spleen. This suggests that IGF-II overproduction induces local effects (auto/paracrine) in the thymic cortex, but not in the thymic medulla. Trabecular growth in the spleen most likely is a distant effect (paracrine or endocrine) of IGF-II overproduction. Accepted: 5 September 1996     

Immunoendocrine modulation and stimulation of hematopoiesis with the ionophore copolymer T150R1

T150R1, an 8000-dalton copolymer with sodium ionophore activity, has been shown to modulate cellular responses in multiple systems. In this article, we studied its effects on lymphoid and hematopoietic organs in the context of the adrenal-pituitary axis. When injected in mice as an oil in water emulsion, T150R1 caused a rapid, profound, and dose-dependent thymic involution accompanied by splenic hyperplasia. Time course experiments with a 2.5-mg dose revealed that the thymus size was minimal at Day 2, rose to normal by Day 14, then enlarged and gradually returned to normal by Week 6 postinjection. Thymic involution was due to cellular depletion of the cortical area, whereas thymic enlargement was due to cortical hyperplasia. Splenomegaly was seen as early as Day 4, peaked by Day 14, and gradually returned to normal by Week 6. The splenic enlargement was due to hyperplasia of the red pulp, with evidence of proliferating erythropoietic, myelopoietic, and megakaryopoietic precursors. In addition, the bone marrow was stimulated and extramedullary hematopoiesis was present in the liver. The effects of T150R1 on the thymus appeared to be mediated by corticosteroids while the effects on hematopoiesis were not. Corticosterone and ACTH levels were increased in treated animals. Adrenalectomy diminished the T150R1-induced thymic involution but enhanced the splenic hyperplasia. Hypophysectomy did not prevent thymic involution, suggesting that T150R1 has endocrine stimulatory effects. These data suggest that T150R1 represents a new class of ionophores which may act on excitable cells within the endocrine, immune, and hematopoietic systems.     

Effect of the thymus on the activity of immunoreactive peptides

Influence of the thymic gland on the biology activity of peptide mediators--cytomedins, has been studied in the content of different organs. The peptide which was obtained from the liver, spleen and muscle of sham-operated animals enhanced immune response on the sheep red cells, lengthened indexes of thromboelastography, and activated fibrinolysis after its administration to the thymectomized rats. The peptides from organs of thymectomized animals lost this ability. These findings confirm the hypothesis on the regulating function of the thymic gland in the synthesis and activity of cytomedins in the tissues.     

Thymic modulation of IL-2 and IL-4 synthesis by peripheral T cells

In this paper we provide several lines of evidence to support the hypothesis that the thymus can exert regulatory influences on the functional capabilities of mature recirculating T cells. Our studies demonstrate that while the IL-2-producing potential of T cells that repopulate the secondary lymphoid organs of lethally irradiated and stem cell-reconstituted mice is significantly reduced compared to that of T cells harvested from normal mice, the amount of IL-4 produced by the T cells of these experimental animals is equivalent to, or greater than, the amount produced by T cells from control animals. In addition, we determined that the amount of biologically active IL-2 and IL-4 secreted by T cells harvested from lethally irradiated animals who reconstitute their hematopoietic and immune systems under the influence of nonirradiated thymic epithelial grafts is essentially identical to the amount produced by T cells harvested from nonirradiated control animals. Collectively, these findings suggest that: (1) the alterations observed in the lymphokine-producing potential of T cells harvested from lethally irradiated and stem cell-reconstituted mice is not due to a direct effect of ionizing radiation on the T lymphocytes themselves, and (2) the exposure of the epithelial cells of the thymus to ionizing radiation during marrow-ablative regimens abrogates or modifies a component of thymic function which can influence the lymphokine-secreting potential of recirculating T cells. Further evidence for thymic involvement in the regulation of lymphokine production by peripheral T cells comes from our finding of a post-thymectomy time-dependent reduction in the capacity of T cells from animals to produce IL-2. Coincident with this reduction, T cells harvested from peripheral lymphoid organs of thymectomized animals demonstrated an augmentation in their IL-4-producing capabilities. The finding that treatment of thymectomized animals with the androgen steroid hormone dehydroepiandrosterone reestablished a normal IL-2-producing potential by their T cells makes it unlikely that the reduced capacity to produce IL-2 was secondary to a loss in fresh thymic emigrants.     

Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (<Emphasis Type="Italic">op</Emphasis>/<Emphasis Type="Italic">op</Emphasis>) mice after macrophage depletion

We previously reported that macrophage colony-stimulating factor (M-CSF, CSF-1) played important roles in the process of the repopulation of Kupffer cells after their elimination by administration of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP). In this study, we examined the repopulation of Kupffer cells and splenic red pulp macrophages in osteopetrotic (op/op) mice defective in the production of functional M-CSF and their littermate mice by using the lipo-MDP model. In untreated op/op mice, numbers of F4/80-positive Kupffer cells in the liver and F4/80-positive splenic red pulp macrophages were reduced. Repopulation of Kupffer cells and splenic macrophages was observed in littermate (op/+) mice liver by 14 days after depletion. However, in op/op mice, repopulation of Kupffer cells was not observed in Kupffer-cell-depleted op/op mice until 56 days after depletion, whereas splenic red pulp macrophages repopulated and recovered to the level of control op/op mice by 10 days after depletion. Single injection of M-CSF was effective for the induction of the repopulation of Kupffer cells, and daily administration of M-CSF induced remarkable repopulation and maturation of Kupffer cells and proliferation of macrophage precursor cells in the liver of Kupffer-cell-depleted op/op mice. These results suggest that Kupffer cells are completely M-CSF-dependent tissue macrophages, whereas splenic red pulp macrophages are composed of M-CSF-dependent macrophages and M-CSF-independent macrophages. This mouse model provides a useful tool for the study of effects of growth factor on Kupffer cell differentiation in vivo. This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan, NIH grant CA20408, and a Tsukada Memorial Grant (2000).     

Bacterial translocation from the gastrointestinal tracts of thymectomized mice

The incidence of translocation of viable indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node, spleen, liver, and kidney was compared in neonatally thymectomized mice and sham-thymectomized specific pathogen-free mice. The immunologic responses of the thymectomized mice to sheep erythrocytes were decreased compared to the responses of sham-thymectomized mice. Strictly anaerobic bacteria were isolated from only 1.8% of the organs from thymectomized mice and from none of the organs of shamthymectomized mice. Aerobic or facultatively anaerobic bacteria were cultured from 27.4% of the organs of thymectomized mice. Of the thymectomized mice, 70.7% contained viable aerobic or facultatively anaerobic bacteria in one or more of their organs tested, compared with only 10% of the sham-thymectomized mice.Escherichia coli was the predominant bacterial species isolated from these organs, althoughStaphylococcus aureus, Streptococcus, andCorynebacterium also were present.Bacteroides were the only strictly anaerobic bacteria cultured. Neonatal thymectomy promotes the translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node, spleen, liver, and kidney.     

Ultrastructural changes in the spleen of the natterjack,Bufo calamita,after antigenic stimulation

Summary In the present study comparative aspects of the ultrastructure of the spleen were analyzed in non-immunized and T-dependent antigen-challenged natterjacks, Bufo calamita. Special attention is focused on the role of the non-lymphoid components in the splenic immunoreactivity. Ten days after primary immunization with sheep erythrocytes, splenic lymphoid follicles increase considerably in number and size. By that time, lymphoblasts, medium and large lymphocytes abound in the periphery of the white pulp near the marginal zone. Meanwhile, in the red pulp numerous monocytes migrating across the sinusoidal walls apparently transform into giant, dendritic-like cells. Twenty days after immunization the splenic lymphoid follicles decrease in number, although certain reactivity persists and numerous plasma cells occur in the cell cords and sinusoids of the red pulp. These results are discussed comparatively with those reported in other lower vertebrates.     

Comparison of lymphocyte production in lymphoid organs and their compartments using the metaphase-arrest technique

Summary Lymphocyte proliferation was studied in normal young anesthetized pigs by the metaphase-arrest technique using vincristine (VCR). In each animal biopsies were taken simultaneously from the thymus, mesenteric lymph nodes, spleen, palatine tonsil and Peyer's patches from the ileum and jejunum. After taking the first samples, 0.25 mg VCR/ kg body weight was injected i.v. and then four more biopsies were excised for up to 3.5 h after VCR. Imprints of the lymphoid organs were evaluated as an overall index for each organ, and histological sections were used to determine the mitotic index in typical B-and T-lymphocyte areas in these organs. In follicles of mesenteric lymph nodes, tonsils and the two types of Peyer's patches a comparable increase in the mitotic index was found, 3.62% per hour. In the corona the increase was also comparable but much lower, 0.43% per hour and in the interfollicular area similarly 0.38% per hour. In the spleen the mitotic rate was 0.69% for the white pulp and 0.42% per hour for the red pulp. In the thymic cortex the mitotic index increased by 0.49% and in the medulla by a surprisingly high value of 0.32% per hour. The metaphase-arrest technique in larger animals enables a comparison of lymphocyte production among organs and their different compartments, and demonstrates the important contribution of peripheral lymphoid organs to the renewal of the lymphocyte pools.List of Abbreviations DNA deoxyribonucleic acid - ¹⁴ C-TdR thymidine labelled with ¹⁴C - ³ H-TdR tritiated thymidine - r _m rate of entry of cells in mitosis per hour - VCR vincristine sulphate Partly presented at the XII Int. Anat. Congress in London, August 1985     

The fate of intraperitoneally injected carbon particles in cyprinid fish

Summary The lymphoid organs of rosy barb (Barbus conchonius) and carp (Cyprinus carpio) were investigated for their phagocytic uptake of carbon, after its intraperitoneal injection. Carbon handling was similar in both species. It was first detected in the lymphoid organs at 30 min after injection. During the first day, carbon was phagocytized by macrophages situated in the spleen within the ellipsoids and in the red pulp. In head and trunk kidney, carbon was found in macrophages scattered throughout the haemopoietic parenchyma, and in cells lining the blood sinuses. In the spleen, macrophages replete with carbon left the ellipsoidal structures and formed aggregates with pigment-containing macrophages from day 6 onwards. In all lymphoid organs, almost all carbon was ultimately concentrated in the melano-macrophage centres.     

Some endocrine aspects of the thymus gland.

In studies of the mouse thymus, lymphocyte mitoses are seen to be most frequent in the thymus cortex. There is evidence from thymic grafts that a hypothetical factor, thymopoietin, may stimulate mitosis of thymic lymphocytes. It is a factor which is postulated to act in conjunction with the PAS-positive mesenchymal reticular cells and epithelial reticular cells of the cortex. The thymus medulla is necessary for the integrity of thymic grafts, and may also elaborate a secretion for maintaining the cellular functions of the gland. Thymectomy has been used as a gauge for judging normal thymic function and results, in the mouse, in lymphopenia, degeneration of spleen and lymph nodes, delayed rejection of skin allografts, reduced ability of spleen cells to mount the graft versus host reaction, and reduced primary immune response to certain antigens. Correction of these deficiencies offers a means of evaluating various thymic extracts and grafts. Lymphocytosis-stimulating hormone (LSH) is known to maintain the peripheral lymphoid organs and cause lymphocytosis in the thymectomized animal. Diffusion chamber studies of thymic grafts also show restored lymphoid tissue by a cell-free factor (CIF). These two factors may be the same and probably represent the basis of the highly purified lymphocyte-stimulating proteins, LSHr and LSHh, which restore the L/P ratio in thymectomized animals and may stimulate lymphopoiesis in spleen and lymph nodes. LSHr, unlike LSHh, increases the total lymphocyte count. LSHr has been found to increase the humoral antibody response in neonatal mice both by the PFC technique and by direct hemolysis of sheep erythrocytes. Homeostatic thymic hormone (HTH) is a thymic extract of small molecular weight and contains nucleic acid. In the thymectomized guinea pig it has been found to maintain normal levels of lymphocytes in the blood, spleen and lymph nodes, to restore antibody titers to typhoid H antigen and to restore the toxic allergic reaction. Thymic humoral factor (THF) is of smaller molecular weight (less than 1,000) and probably is not a protein. It also enhances lymphoid proliferation in neonatally thymectomized mice. There is evidence that THF participates in humoral antibody formation because it stimulates PFC formation from neonatally thymectomized mice after inoculation with sheep erythrocytes. Its effects on cell-mediated immunity are seen from findings that injection of THF restores the ability of thymectomized mice to reject skin allografts. THF enables spleen cells from thymectomized or neonatal animals to mount the graft versus host reaction, and causes maturation of bone marrow cells and spleen or lymph node cells so that they can participate in the graft versus host reaction. It has been reported to stimulate lymphocytes to kill isogeneic tumor cells in vitro. Thymosin is protein extracted from the thymus. It has been found to alleviate leukopenia slightly and provide some improvement in lymphoid histology in thymectomized mice...     

Suspension of thymic emigration promotes the maintenance of antigen-specific memory T cells and the recall responses

Thymic involution is evolutionarily conserved and occurs early in life. However, the physiological significance remains elusive of this seemingly detrimental process. The present study investigated the potential impact of altered thymic output on T cell memory using ovalbumin (OVA) expressed by Listeria monocytogenes as a model antigen. Suspension of thymic emigration by thymectomy was shown to lead to a marked increase in the frequency and total number of OVA-specific memory T cells. In contrast, oversupply of thymic emigrants through thymic grafting caused a significant decrease of such cells. When rechallenged with L. monocytogenes expressing OVA, the thymectomized mice mounted a more potent recall response as evidenced by the enlarged population of OVA-specific tetramer⁺ cells and the accelerated clearance of the bacteria. Notably, the memory-enhancing effect of thymectomy was abrogated following weekly adoptive transfer of naive T cells. Together, data from the present study indicate that reduced thymic output favors the maintenance of the memory T cell pool.     

Immune response of mice exposed to cis-diamminedichloroplatinum

Summary The effects of cis-diamminedichloroplatinum (CDDP) on lymphoid organs and the immune response of young and older adult mice were studied histologically and by functionally assessing the activity of various subpopulations of immune cells. Young adult mice (6–8 weeks old) treated with 2 mg/kg CDDP mounted an enhanced splenic plaque-forming cell (PFC) response to both sheep erythrocytes, a helper T-cell-dependent antigen (HD), and pneumococcal polysaccharide type III a helper T-cell-independent antigen (HI). Older adult mice (18–22 weeks old) treated in the same way exhibited an equally enhanced PFC response to HD antigen and even a more pronounced response to HI antigen. Treatment of mice with 12 mg/kg CDDP resulted in immunosuppression. Thymus, lymph nodes, and spleen of animals treated with the higher dose of CDDP showed a marked cell depletion from both T and B areas, confirming that the immunosuppression was due to an indiscriminate elimination of both T and B lymphocytes. The immunosuppression and the cell depletion from lymphoid organs were more pronounced in younger mice. Thus, the effects of CDDP on the lymphoid organs and the immune response depend both on the age of the animals and on the dose of the drug. CDDP given in small doses enhances the PFC response, whereas a reduced PFC response is obtained following high-dose treatment. Abbreviations used: CDDP, cis-diamminedichloroplatinum; PFC, plaque-forming cell; HD, helper T-cell dependent; HI, helper T cell-independent; SIII, pneumococcal polysaccharide type III; SRBC, sheep red blood cells; TNP, trinitrophenyl; KLH, keyhole limpet hemocyanin; TNBS, 2, 4, 6-trinitrobenzene sulfonic acid; BBS, borate-buffered saline     

The effect of bursectomy and thymectomy on the course of avian influenza virus infection

The effect of hormonal bursectomy and neonatal surgical thymectomy on the course of an avian influenza virus infection in chickens was studied. Analysis of the immunologic status of the chickens prior to infection included assay of natural agglutinins to rabbit red blood cells and induced agglutinins to sheep red blood cells, serum immunoelectrophoresis patterns, and in vitro effects of phytohemagglutinin on lymphocyte transformation. At 6 wk of age the chickens received the influenza virus intratracheally. Daily temperatures and mortality were recorded and HAI antibody titers were measured 7 and 14 days later. Completely thymectomized chickens were characterized by a failure of lymphocyte transformation to take place in two successive studies and absence of thymic remnants at autopsy. Bursectomy was associated with a significantly higher occurrence of temperature elevation (P < 0.05) and mortality (P < 0.001). Thymectomy had no significant effect on the course of the virus infection. Preliminary findings with passive administration of serum from immune animals also suggested a role for antibody in host resistance. These studies suggest cell-mediated immunity is less important than humoral immunity in recovery from avian influenza virus infection.     

Trypanosoma cruzi: early resistance induced by culture-derived trypomastigotes

Previous observations in this laboratory showed that injection of culture-derived trypomastigotes (CT), in CBA/J mice, induced an early increased resistance that was detected 24-72 hr after antigen injection and permitted mice to survive a challenge of 10(5) blood trypomastigotes (BT) corresponding to 2000 LD50%. Present experiments were conducted to determine the optimal conditions for inducing this early resistance and to investigate the early morphological changes which occurred in blood and lymphoid organs of mice infected with either BT or CT. Among nine antigens tested, only living CT showed a protective effect permitting most of mice to survive 30 days after BT challenge, while control mice injected with PBS or other antigens died at 10 +/- 1 days. A dose-response relationship was seen when different doses of CT were tested, higher doses of CT inducing higher survival and lower parasitemia. Injection of CT by either an im or ip route induced similar degrees of resistance but significantly different results were obtained when mice were challenged by using ip or im routes. Higher parasitemia and lower survival were always obtained when animals were challenged by the ip route. Within 72 hr, mice injected with BT presented a lymphopenia which reached a maximum at 48 hr, a depletion of thymic cortical zone, and splenomegaly with hyperplasia of the white pulp and congestion of the red pulp. No gross alterations were observed in animals infected with CT. Overall data suggest that the early resistance is a specifically induced phenomenon and that BT and CT induce different early reactions in the CBA/J lymphoid organs.(ABSTRACT TRUNCATED AT 250 WORDS)     

White pulp compartments in the spleen of the turtle Mauremys caspica

Summary The aim of the present study was to analyze the nature of lymphoid and non-lymphoid cellular components occurring in distinct histological compartments of the splenic white pulp of the turtle, Mauremys caspica, in order to define their possible correlations with those of the spleen of higher vertebrates, principally mammals. The white pulp of M.caspica consisted of 3 clearly distinguishable regions: (1) the periateriolar lymphoid sheath, and (2) the inner and (3) the outer zones of the periellipsoidal lymphoid sheath. Reticular cells intimately associated with reticular fibres constituted an extensive meshwork in the periarteriolar lymphoid sheath which housed principally Ig-negative lyphoid cells, mature and immature plasma cells, and interdigitating cells. A few Ig-positive cells were also present in the peripheral region of the periarteriolar lymphoid sheath. The inner and outer zones of the periellipsoidal lymphoid sheath were separated by a discontinuous layer of reticular cell processes. In the inner zone, surface Ig-positive lymphoid cells predominated as well as dendritic cells, resembling ultrastructurally the mammalian follicular dendritic cells, although no germinal centres were found in the turtle spleen. Macrophages, some cytoplasmic Ig-positive cells, and Ig-negative lymphoid cells appeared in the outer zone of the periellipsoidal lymphoid sheath. These results allow us to speculate on a phylogenetic relationship between the periarteriolar lymphoid sheath and the inner and the outer zones of the periellipsoidal lymphoid sheath of the spleen of M. caspica and the periarteriolar lymphoid tissue, the lymphoid follicles and the marginal zone, respectively, of the mammalian splenic white pulp.     

Thymic and splenic changes following injection of living Brucella and BCG in the Guinea pig

Summary The thymic and splenic reactions, following injections of BCG and living Brucella M. in the guinea pigs, were studied. Both microorganisms injected intravenously produced thymic involution, maximal after BCG inoculation, followed by regeneration that was complete by day 10 in Brucella M.-treated guinea pigs, and by day 15, in BCG injected guinea pigs. Increase of mitotic index was more accentuated and more persistent after Brucella M. than after BCG treatment in the thymus. After a short involution period the spleen of injected animals increased in size in both groups. The splenic enlargement was dramatic and occurred at an accelerated rate in animals given BCG. It appeared to be the result of a conspicuous involvement of the red pulp by multiple granulomas. In Brucella M. treated guinea pigs the splenic enlargement was less obvious, but the splenic white pulp was more abundant in BCG-treated guinea pigs. Granulomas were observed only in the periarterial sheaths of the white pulp.These observations provide evidence for the hypothesis that injections of both BCG and Brucella M. provoke a proliferation of B and T lymphocytes, a migration of T lymphocytes from the thymus to the T-dependent area of the spleen which seems, perhaps, more marked after injection of Brucella M., and a strong granulomatous histiocytic reaction which is more conspicuous in animals given BCG.     

Immunoregulation mediated by the sympathetic nervous system,II

The effect of acute immunization or continuous environmental antigenic exposure on nor-adrenaline (NA) content of rat lymphoid organs was studied. Immunization with sheep red blood cells resulted in a decrease in splenic NA content. In other experiments, NA levels were determined in lymphoid and nonlymphoid organs of SPF rats exposed to naturally occurring environmental antigens, as well as in germ-free animals of the same strain. Spleen, thymus, and lymph nodes in SPF rats contained about 50% less NA than germ-free animals. With the exception of the adrenals, nonlymphoid organs showed no such a difference. Taken as a whole, the present results and our previous data on immunosuppressive influences of the sympathetic innervation on lymphoid organs support the notion that the sympathetic system plays a role in immunoregulation.     

Immune suppression and histophysiology of the immune response

Seven daily intramuscular (im) injections of cortisone acetate (25 mg/Kg b.w.) given to rats or rabbits produced, (i) a pronounced reduction in the numbers of small lymphocytes in thymus-independent areas, (ii) atrophy of the thymic cortex, (iii) atrophy of germinal centres and (iv) a consequent depressed production of germinal centre-derived cells. Lymphocyte depletion was not caused by cell lysis. Moreover cell traffic between peripheral lymphoid organs did not seem to be altered. A revival of the depressed germinal centres in cortisone-treated (inbred) rats could be achieved by a transfer of bone-marrow cell suspensions from normal, cortisone-treated or T-cell-deprived animals. It was concluded that cortisone acetate arrests the migration of B-lymphocytes from the bone marrow to germinal centres in peripheral lymphoid organs, and that the accumulations of lymphoid cells in the bone marrow of cortison-treated animals might be composed of immature or mature T- and B-lymphocytes.