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Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice.

Neonatal thymectomy of mice, when no ectopic thymus existed, constantly resulted in developmental arrest of the ovary but not of the testis; it also caused sterility in the female. The ovaries of thymectomized mice were extremely small and were characterized by absence of follicles and corpora lutea. Such an ovarian dysgenesia was observed when the mice were thymectomized at 3 days of age, but not at 7 days or later; it was prevented by thymus grafting.

Animals↗

Neonatal thymectomy increases the incidence of spontaneous and methylcholanthrene-enhanced thyroiditis in rats.

At 16 weeks of age, 13 percent of untreated Buffalo strain rats showed evidence of autoimmune thyroiditis. Feeding methylcholanthrene increased the incidence to 42 percent. Neonatal thymectomy significantly raised the incidence of disease so that almost all (87 percent) untreated and all methylcholanthrene-treated animals developed severe disease. It is proposed that the thymus exerts a regulatory effect on autosensitization.

Age Factors↗

Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus.

In B6AF1 mice, T lymphocytes that use the V beta 11-positive (and not V beta 6-positive or V beta 8-positive) segment in their receptor for antigen are greatly reduced in the thymus and peripheral lymphoid tissues, most likely as a result of clonal deletion. The relative number of V beta 11-positive cells in adult lymph nodes was ten times as high in B6AF1 mice thymectomized 1 to 4 days after birth as in normal mice. Moreover, for the first 10 days of life of B6AF1 mice, mature V beta 11-positive T cells were readily detected in the thymus and spleen. Thus neonatal thymectomy results in the maintenance of the receptor repertoire of early postnatal life, and this correlates with the subsequent development of organ-specific autoimmune diseases.

Animals↗

Effect of thymectomy and antilymphocyte serum on Mycobacterium leprae infection in mice.

BALB/c mice thymectomized at 3 to 5 days of age were studied to determine if this procedure would result in enhanced susceptibility to infection with Mycobacterium leprae and, if so, whether or not administration of antilymphocyte serum would further increase this susceptibility. The plateau for growth in the footpads of intact mice occurred 4 months after inoculation, whereas in the thymectomized and thymetocomized plus antilymphocyte serum-treated groups the plateau occurred between months 11 and 12 after inoculation. Thymectomy resulted in at least a 10-fold increase in the number of M. leprae found in the footpads. Antilymphocyte serum did not appear to further enhance the M. leprae infection in the thymectomized mice. Although growth of M. leprae in the testes of both intact and thymectomized mice was erratic, the number of organisms reached a higher ceiling in the thymectomized groups. M. leprae harvested from all groups was passaged into intact mice at various intervals after inoculation to test for viability. Viable M. leprae were found at all intervals tested including 22 months after infection in the intact mice, suggesting that a chronic infection occurred that probably lasted during the entire life of the animals.

Animals↗

Effect of neonatal thymectomy on immune responses of rats to Streptococcus mutans.

The effect of neonatal thymectomy on secretory and systemic antibody responses in rats was studied. Groups of normal or thymectomized (Tx) rats were infected or immunized and infected with Streptococcus mutans 6715. Tx rats exhibited a significantly lower level of salivary immunoglobulin A (IgA) antibody to S. mutans after a 45- to 65-day infection. Similarly, after multiple local injections of formalinized S. mutans, Tx rats showed a delay in the appearance and lower levels of salivary IgA antibody to S. mutans. Serum IgG antibody levels were also decreased in Tx rats with both experimental protocols. In contrast, salivary IgG and serum IgM anti-S. mutans activity in Tx and normal rats were similar during the experiments. These results demonstrated that thymus deprivation at birth produces profound effects on the ability of rats to manifest secretory IgA antibody responses to the pathogenic microorganism S. mutans.

Animals↗

Induction of an organ-specific autoimmune disease, lymphocytic hypophysitis, in hamsters by recombinant rubella virus glycoprotein and prevention of disease by neonatal thymectomy.

Glycosylated, membrane-associated E1 (58-kDa) and E2 (47- to 49-kDa) rubella virus proteins and unglycosylated nucleoprotein C (33 kDa), from separately expressed vaccinia virus recombinants, were injected into golden Syrian hamsters. Rubella virus E1 and E2 glycoproteins consistently induced an organ-specific autoimmune disease, autoimmune lymphocytic hypophysitis, which was evidenced by the induction of autoantibodies against pituitary cells and by lymphocytic infiltration of the pituitary. Neonatal thymectomy prevented the disease. In contrast, rubella virus nucleoprotein C did not induce either autoantibodies against pituitary cells or lymphocytic infiltration of the pituitary. This finding raises the possibility that virus-specific protein itself can induce an organ-specific autoimmune disease in certain circumstances.

Animals↗

Crohn's disease and myasthenia gravis: a possible role for thymectomy.

A female patient with a three year history of Crohn's disease of the colon developed myasthenia gravis. Despite diversion of the faecal stream by an ileostomy, and total colectomy, the patient had continuing problems with perineal and perianal abscesses and fistulas. Her myasthenia gravis became unresponsive to anti-cholinergics so a thymectomy was performed. The perineal and perianal disease improved subsequently. This case supports the theory that functional disturbances of the thymus may have a role in the pathogenesis of inflammatory bowel disease.

Adult↗

Myasthenia gravis: clinical and histological features in relation to thymectomy.

The clinical and thymic histological features of 23 patients who underwent thymectomy for myasthenia gravis have been examined and compared. Eighty-two per cent of patients with a non-neoplastic gland containing numerous germinal centres improved postoperatively, whereas 83% of patients with a non-neoplastic gland containing no germinal centres deteriorated or died. Glands with only slight involution and containing numerous germinal centres were more commonly seen in young female patients. The evidence relating thymic histological appearances with the postoperative progress of patients with myasthenia gravis is reviewed.

Adolescent↗

Thymectomy in myasthenia gravis during pregnancy.

A 24 year old woman with myasthenia gravis suffered an antepartum exacerbation which failed to respond to increasing dosages of pyridostigmine. Thymectomy performed in the second trimester was followed by clinical improvement and full term vaginal delivery with no puerperal deterioration.

Adult↗

Time course of serum glucoregulatory variables and lipids following neonatal thymectomy of diabetes-prone and control BB Wistar rats fed a defined diet.

The acute diabetic syndrome in the BB Wistar rat resembles human type 1 (insulin-dependent) diabetes, including a possible association with T cell-mediated, (auto)immune processes. In most previous studies 'normoglycemic' littermates of diabetic BB rats have been used as controls and little attention has been paid to the role of diet. It now appears that asymptomatic/diabetes-prone littermates of diabetics have immune system defects as well as metabolic abnormalities. Since there are also indicators that the disease process starts before animals become symptomatic, we looked for prospective metabolic changes in prediabetic, asymptomatic/diabetes-prone and control (diabetes-free) BB rats following intervention in the immune system while maintaining the animals on a defined diet (AIN-76). The results reported here confirm and extend the finding of Like et al. (1982) that neonatal thymectomy reduces the frequency of the syndrome and emphasize the role of diet in modifying its expression. In contrast to previous reports of hyperglucagonemia only after onset of diabetes, asymptomatic/diabetes-prone animals had periodic increases of plasma glucagon values up to 3-fold those of diabetes-free controls; prediabetics displayed a similar pattern. Asymptomatic/diabetes-prone rats also tended to have slightly higher blood cholesterol levels. The low incidence and delayed onset of the syndrome in rats fed a modified AIN-76 diet (27%, 127 +/- 21 days) compared to the previous chow-fed generation (60%, 93 +/- 18 days) and chow-fed littermates (38%, 87 +/- 16 days) suggested that diet can modify expression of the syndrome.

Animals↗

Neonatal thymectomy diminishes renal IgA deposition in IgA nephropathy-prone ddY mice.

To understand the role of thymus-derived T cells in the development of IgA nephropathy (IgAN), we performed neonatal thymectomies on ddY mice, in which this disease occurs spontaneously. Although these thymectomized mice developed a renal lesion closely resembling that typical of IgAN, the extent of their mesangial IgA deposition was significantly milder than in control sham-operated mice. The immunological mechanisms responsible for curbing this mesangial deposition of IgA were then analyzed. The percentage of splenic T cells and the magnitude of mitogenic responses both decreased markedly in thymectomized compared with control mice. These results suggested the hypofunction of thymus-derived T cells. However, serum IgA levels were almost identical in both groups. Furthermore, sera from both groups contained similar amounts of macromolecular IgA, of the type formerly eluted from the affected glomeruli of patients with IgAN. These results strongly indicate that thymus-derived T cells or their products determine the amount of IgA deposited in the kidneys of ddY mice.

Animals↗

The effects of late thymectomy on the immunosuppressive action of cortisone and testosterone in rats immunized to sheep red blood cells.

The immunological effects of cortisone and testosterone were studied in intact and lately thymectomized rats immunized to sheep red cells. The results showed that the effects of low doses of cortisone as well as those of high doses of testosterone (drop in the total number of rosette- and plaque-forming cells: RFC and PFC) were conditioned by the involution of the thymic cortex provoked by such hormonal doses, since these changes did not occur in thymectomized rats. The effects of high doses of cortisone were partly not influenced by thymectomy (drop in the RFC and PFC levels) but partly thymus-dependent (drop in the serum antibody titers). The latter were apparently related to advanced lesions of the thymic medulla.

Animals↗

Observations on rosette formation by thymocytes and T lymphocytes in guinea pigs. Effect of neonatal thymectomy, irradiation, thymosin, albumin and the influence of cell viability.

Irradiation (300 rad) of guinea pigs and subsequent transfer of bone marrow cells was followed by a decreased frequency of rabbit erythrocyte rosettes (a T lymphocyte marker) in peripheral lymphoid organs. Neonatal thymectomy did not potentiate this effect. A reduced amount of rosette-forming cells was also found in the thymus of irradiated animals. This was not affected by treatment with thymosin in vivo or in vitro, and was probably due to a reduced viability of the cells after irradiation since it was demonstrated that rosette formation among dead thymus cells was significantly less than among living cells. Incubation of normal thymocytes in non-supplemented medium for 2--4 h at 37 degrees C was also followed by a diminished rosette-forming capacity. The addition of thymosin or bovine serum albumin prevented both the decrease of rosette-forming cells and the reduction of viable cells during incubation. Thus, a diminished rosette formation may have been caused by reduced viability after incubation as well as after irradiation. The rosette-forming ability of only some dead thymocytes may reflect different subpopulations.

Animals↗

Outcome after thymectomy for myasthenia gravis: a retrospective review.

This is a retrospective study of 54 patients, who in the period November 1977 to November 1986 underwent thymectomy as treatment for myasthenia gravis. Patients in whom difficulty attempting complete excision of the gland was anticipated were selected for a transthoracic procedure. All others underwent an initial transcervical approach, proceeding to an upper sternal splitting incision if further access was required to remove adequately a large gland. The sample was split almost equally between the two surgical procedures. Patients in the transthoracic group were significantly older and experienced significantly greater peri-operative morbidity or mortality. There was no significant difference in outcome between the two groups, 52% achieving a good result (defined as remission or clinically significant improvement of symptoms) that was sustained over the five year follow-up period. In our opinion, complete removal of the thymus should be the goal of surgical treatment for myasthenia gravis.

Adult↗

Isoflurane for thymectomy in myasthenia gravis.

The clinical and electromyographic effects of isoflurane were studied in eight myasthenic patients undergoing trans-sternal thymectomy. After inhalational induction of anaesthesia, intubating and operating conditions were good. Recovery from anaesthesia was rapid with minimal postoperative residual muscle weakness or respiratory depression. All patients were extubated within the first postoperative hour. Integrated electromyographic monitoring of the train-of-four response of adductor pollicis demonstrated that myasthenics are more sensitive than nonmyasthenics to the neuromuscular depressant effects of isoflurane. Recovery of the integrated electromyographic response was incomplete despite a satisfactory clinical recovery.

Adolescent↗

Remifentanil and propofol total intravenous anaesthesia for thymectomy in myasthenia gravis.

We report a case of trans-sternal thymectomy for myasthenia gravis using a non relaxant, total intravenous technique with propofol and remifentanil. This afforded excellent control of heart rate and pressor responses during surgery while allowing early return of spontaneous ventilation and extubation within nine minutes of termination of anaesthesia. Advantages and disadvantages of this approach versus relaxant and volatile techniques are discussed with particular reference to preservation of neuromuscular function.

Adolescent↗

Shifting of the blood T:B lymphocyte ratio in myasthenia gravis patients after thymectomy.

The immunologic role of thymus in human adults is still unclear, in a high percentage of patients with myasthenia gravis, improvement of the disease follows thymectomy. The biologic basis of this phenomenon is also unknown. We found that patients thymectomized for more than 9 months have a low percentage of T cells (mean 34 percent). The mean T cell percentage in control myasthenia gravis patients is 52 percent. Patients thymectomized for more than 18 and 24 months exhibit values of T cell percentage not lower than those of patients thymectomized for more than 9 months. Our results may be interpreted according to a humoral action of the thymus in regulating the percentage of T lymphocytes.

Adolescent↗

Serum antibodies to cytomegalovirus in myasthenia gravis: effects of thymectomy and steroids.

The etiology of the immunologic abnormalities in myasthenia gravis (MG) remains unknown. Evidence for persistent viral infection was sought by determining serum antibody titers to several enveloped RNA and DNA viruses. Compared to healthy controls matched for age, sex, geography and socioeconomic status, patients with MG were more likely to have elevated titers of complement-fixing antibody to cytomegalovirus (CMV). Patients with MG not treated with thymectomy or steroids had elevated CMV titers, whereas thymectomized or steroid-treated patients did not; the differences were statistically significant (p less than 0.01). These results are consistent with the hypothesis that there is persistent viral antigenic stimulation in the myasthenic thymus, arising from viral protein incorporation into epithelioid-myoid cell surface membranes and subsequent induction of an antibody to these acetylcholine receptor (AChR)-bearing thymic cells. This antibody then cross-reacts with AChR at the neuromuscular junction.

Adult↗