Experimental autoimmune prostatitis after neonatal thymectomy in the mouse.

Experimental autoimmune prostatitis (EAP) could be induced in (C3H/HeMs X 129/J)F1 mice by thymectomy (Tx) at 3 days (Tx-3) but not at 0 or 7 days after birth. Appearance of EAP was noticed in the three lobes of the prostate, most frequently and severely in the anterior lobe (coagulating gland). EAP thus induced was characterized by a loss of secretory products in the lumen, massive lymphocytic infiltration in the stroma, especially beneath the epithelial cells, and by the presence of circulating autoantibody(ies) against the epithelial cells of the prostate (APA). EAP started at puberty and its incidence was 68% in 50-150 day old mice. APA was completely absorbed with the homogenates of prostate but not of seminal vesicles, testes or livers of the mouse. High titres of APA, detectable in sera of more than 1,000-fold dilutions accompanized with the severe lesion, were assayed by indirect immunofluorescence (IFL) technique. No sign of EAP was seen in the immature prostate of 90 day old mice which were orchidectomized at 0 day (Orx-0) followed by Tx-3. Exogenous androgen treatment at an adult age induced EAP in these Orx-0 plus Tx-3 mice. The findings indicate that mice which received Tx at a critical neonatal age develop EAP by autosensitization to the antigen(s) normally expressing in the differentiated prostate.     

Experimental autoimmune orchitis after neonatal thymectomy in the mouse.

Experimental autoimmune orchitis (EAO) developed in (C57Bl/6Cr x A/JCr)F1 mice 3-4 months after neonatal thymectomy (Tx) without any sensitization. The age of Tx was critical for induction of EAO: Tx at day 3 (Tx-3) was effective, but Tx at day 0 or day 7 was not effective. This lesion resulted in atrophy of the testis and was characterized by disappearance of mature sperms, formation of multinuclear giant cells in seminiferous tubules and infiltration of lymphocytes in the stroma. Epididymitis was observed prior to the development of EAO. Presence of circulating autoantibody(s) against sperms (ASA) was demonstrated by indirect immunofluorescence. The acrosomal area of mature sperms, but not of immature spermatids, was strongly. The incidence of EAO and titre of ASA increased when Tx-3 mice were unilaterally vasectomized (Vx). The majority of mice with high titres of circulating ASA were sterile. Epididymitis and orchitis could be prevented in Tx-3 mice by injection of adult spleen cells on day 4. The most effective source was normal male. Spleen cells from normal female donors and day-0 orchidectomized (Orx) donors were less effective, while those of Tx-3 male and female donors failed to prevent epididymis and orchitis. The cell population in normal male spleen effective in preventing epididymitis was shown to be a T cell population (Thy 1+, Ig-) by experiments with respective antisera treatment. These results showed that sensitization with sperm autoantigen occurred in the epididymis after Tx-3, more efficiently after Tx-3 plus unilateral Vx, and that this autosensitization was prevented by a specific suppressor T cell population, which was present in normal males but absent in Tx-3 mice.     

Structural and immunologic parameters of peyer's patches in the human fetus

Laboratory of Embryonic Histogenesis, Research Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 5, pp. 621–623, May, 1988.     

Regeneration of the rabbit spleen after hydrocortisone injection

The action of hydrocortisone on the rabbit spleen and the regenerative processes arising after cessation of administration of the hormone were studied. During prolonged administration of hydrocortisone the absorptive function of the reticuloendothelial system is depressed and atrophy of the spleen develops, as shown by a reduction in the weight and size of the organ. Most of the splenic follicles are converted into random clusters of lymphocytes. Pyroninophilic cells disappear from the white pulp. After cessation of the action of the hormone the animal's general condition improves, the development of the atrophic changes in the spleen is halted, the splenic follicles are restored, and the number of pyroninophilic cells in them increases. The use of a regeneration stimulator under these conditions accelerates recovery of the body weight of the animal, reversal of the atrophy of the spleen, and restoration of its normal structure.Department of Histology and Pathological Anatomy, Erevan Zooveterinary Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 12, pp. 722–725, December, 1977.     

Modification of the tolerant state by neonatal thymectomy.

Immunological tolerance of sheep erythrocytes was induced by repeated antigenic challenge of rats which had been thymectomized on the day of birth. Thoracic duct lymphocytes from these thymectomized tolerant rats failed to mount adoptive responses against sheep erythrocytes and interfered with the capacity of normal lymphocytes to mount such responses. However, in sharp contrast with non-thymectomized tolerant rats, thymectomized animals responded well to sheep erythrocytes if challenge was accompanied by the injection of normal syngeneic lymphocytes. It is likely that the cells that are lacking from tolerant rats as a consequence of neonatal thymectomy are identical with the radiosensitive cells that suppress normal lymphocytes transferred to intact tolerant rats.     

Penetration of colloidal carbon through post-capillary venules in lymph nodes and peyer's patches of the guinea-pig: a potential immunogeneic route.

Colloidal carbon injected intravascularly provided a selective marker for post-capillary venules in lymph nodes and Peyer''s patches. In the first few minutes a denticulate outline to the lumen was formed by carbon capping the high columnar epithelium and carbon particles were deeply embedded between endothelial cells. Ten minutes after injection carbon had reached the basement membrane and was lying outside this membrane 30 min later, at first free but later engulfed inside macrophages. Carbon was retained in post-capillary venules for the duration of the experiment (8 h). Discontinuities were present in the basement membane in about one-fifth of venules, and lymphocyte and macrophage penetrating the basement membrane are demonstrated. It is postulated that carbon penetrates the post-capillary venular wall by increased intraluminal hydrostatic pressure arising from contraction of muscles that surrounded the lymphoid tissue in the case of the gut, or skeletal muscle compressing lymph nodes against a bony surface in the axilla, groin or neck. Secondly, if carbon is a model for particulate antigens, then post-capillary venules provide a potential immunogenic route whereby antigens can reach lymphoid tissues from the circulation, as proposed by Burwell (1962) for transplantation antigens.     

Involution and regeneration of the mouse thymus after lipopolysaccharide injection

N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 3, pp. 280–283, March, 1990.     

Chemiluminescence of the mouse liver after injection of glucose

The spectral composition of radiation from the mouse liver was studied in situ after intravenous injection of various doses of glucose. A statistically significant ultraviolet component-mitogenetic radiation-appeared after injection of 15 mg glucose. Only visible radiation was recorded after smaller or larger doses. The results are evidence of the role of unbalanced molecular constellations in the regulation of hepatocyte metabolism.     

Freeze-mount microautoradiographic study in the mouse hippocampus after intravenous injection of tritiated 2-deoxyglucose and glucose

Differences in the uptake of tracers from radioactive 2-deoxyglucose ([1,2-3H] and [2,6-3H]), and glucose ([1-3H], [3-3H]) into hippocampal regions were investigated by freeze-mount microautoradiography after 45 min for 2-deoxyglucose, and after 15 and 45 min for glucose. Silver grains were assessed quantitatively by an image analyser. (1) The radioactivity (silver grains/mm2) in the stratum lacunosum-moleculare of Ammon's horn from 2-deoxyglucose autoradiograms was significantly higher than that in other hippocampal regions (P less than 0.01), while lowest in the hilus fascia dentata (P less than 0.01). (2) Autoradiograms of [1-3H]glucose and 15 min of [3-3H]glucose showed the radioactivity in the dentate molecular layer to be significantly higher than that in other regions, excepting the stratum lacunosummoleculare (P less than 0.05). (3) The 2-deoxyglucose and 45-min glucose autoradiograms showed intensely labeled perikarya of pyramidal cells in the CA3a sector. (4) Radioactivity in the dentate granular layer from the 45-min autoradiogram of [3-3H]glucose was significantly higher than that in the molecular layer (P less than 0.05). The results imply that the metabolic fate of glucose, i.e. whether it is mainly used for energy production or amino acid synthesis, depends on each structure of the hippocampus.     

Expression of a gastric autoantigen in pancreatic islets results in non-destructive insulitis after neonatal thymectomy

Autoimmune gastritis, induced by day-3 thymectomy of BALB/c mice, is a destructive CD4⁺ T cell-mediated disease characterized by leukocyte infiltrates in the gastric mucosa, loss of parietal and chief cells and anti-gastric H/K ATPase autoantibodies. Our previous studies have indicated that a T cell response to the H/K ATPase β subunit is required for the onset of autoimmune gastritis (Alderuccio, F., Toh, B. H., Tan, S. S., Gleeson, P. A. and van Driel, I. R., J. Exp. Med. 1993. 178: 419). To determine whether a response to the β subunit autoantigen is alone sufficient to induce autoimmunity, or whether other tissue-specific factors are required, we have generated transgenic mice expressing the gastric H/K ATPase β subunit in β islet cells of the pancreas (RIP-H/Kβ). RIP-H/Kβ mice developed autoimmune gastritis and insulitis after day-3 thymectomy. Significantly, insulitis, observed as a peri-islet infiltrate, was only detected in thymectomized mice with autoimmune gastritis. There was no apparent immune destruction of the pancreas as insulitis did not progress to invasion of the islets or diabetes. Double transgenic mice, expressing the gastric H/K ATPase β subunit in the thymus and in the pancreas, were protected from both gastritis and insulitis after day-3 thymectomy. Therefore, insulitis in the RIP-H/Kβ mice appears to be dependent on a T cell response to the H/K ATPase β subunit. This is the first example where an organ-specific initiating autoantigen has been expressed in another peripheral tissue. Autoimmune destruction in the stomach, but not the pancreas, indicates that tissue-specific factors play a fundamental role in the development of organ-specific autoimmunity.     

Antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat

Genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strains have been simultaneously selected according to their systolic blood pressure (SBP). SBP and immunological parameters were investigated in 5 week-old rats. SBP reached 99 +/- 2 mmHg in LL, 108 +/- 2 mmHg in LN and 122 +/- 4 mmHg in LH. White blood cell and lymphocyte counts, thymus and spleen histology, percentages of T cells and subsets of T cells in these organs were not modified by genetic hypertension. The blastogenic responses to mitogens (Con A and PWM) of the LH rat thymocytes were similar to those observed in LN or LL rats. By contrast, the proliferative response of splenocytes to PWM was positively correlated (r = 0.93) with SBP level. In additional experiments we demonstrated that, besides the immune defect induced by neonatal thymectomy, the removal of the thymus at birth prevented the spontaneous increase of SBP in LH strains (102 +/- 2 mmHg instead of 122 +/- 4 mmHg), while only a slight decrease or no alteration was seen in LN and LL thymectomized rats. This antihypertensive effect tended to maintain SBP at a common level in the 3 strains. These results suggest that the thymus may be involved in the development of genetic hypertension.     

Modifications of the structures of the rat lymph nodes by neonatal thymectomy

Until recently, the deep cortex of the lymph node was thought to exist as a layer completely underlying the peripheral cortex. It was known, moreover, that through neonatal thymectomy, the lymphocyte population of the deep cortex could be depleted. Through our current research, however, we have demonstrated that the deep cortex actually consists of hemispherical 'units'. Each unit is centered under an opening of an afferent lymphatic and comprises a center and a periphery with different morphological features and functions. In the light of this new knowledge, we felt it appropriate to reexamine the influence of neonatal thymectomy on node histology. Rats were thymectomized 5 h after birth. When they were 8 weeks old, nodes from various anatomical sites were submitted for morphological analysis. The resulting observations were compared to those made with nodes of nude as well as normal rats. It was found that the histological changes induced by neonatal thymectomy were comparable to those resulting from the congenital athymic state, but with marked differences. Differences were also observed in the nodes of thymectomized and semi-thymectomized rats. The discussion deals with these differences and presents new observations.     

Kinetics of colony-forming ability of mouse bone marrow cells after administration of hydrocortisone

The dynamics of the colony-forming and migration capacity of polypotent hematopoietic stem cells in the bone marrow of (CBA×C57BL) F₁ mice was studied after injection of hydrocortisone. The relative number of hematopoietic stem cells in the bone marrow was higher than in the control on the 3rd day after hydrocortisone injection. This increase was maximal on the 5th day after the injection. On the 8th day the number of hematopoietic stem cells was down to normal again.Institute of Clinical and Experimental Medicine, Siberian Branch, Academy of Medical Sciences of USSR, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1102–1104, September, 1976.