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PubMed2005

Host thymectomy and cyclosporine lead to unstable skin graft tolerance after class I mismatched allogeneic neonatal thymic transplantation in mice.

BACKGROUND: Our laboratory has demonstrated that xenogeneic porcine thymus tissue grafted in thymectomized (ATX) and T cell-depleted mice induces donor-specific tolerance. Recipient thymectomy is essential for the success of tolerance induction. In contrast, studies in pigs grafted with non-vascularized allogeneic class I mismatched thymus tissue under the cover of CyA have shown that removal of host thymus is detrimental to thymic graft survival. To determine the requirements for nonvascularized allogeneic class I-mismatched thymic engraftment in mice, we performed thymic allotransplantation under the cover of CyA. MATERIALS AND METHODS: Euthymic and ATX B10.MBR mice received class I mismatched B10.AKM neonatal mouse thymus (NMTHY) tissue under the kidney capsule with or without a short course of CyA. The grafts were allowed to engraft for two and a half months before exploratory laparotomy was performed to evaluate them. Three months after the thymic transplant, mice were challenged with donor-specific skin grafts to assess tolerance. One month after donor-specific skin grafting, they received third party B10.BR skin grafts. Cellular anti-donor immune responses were studied at the time of euthanasia. RESULTS: CyA-treated ATX and euthymic control mice showed good engraftment of the allogeneic thymic tissue at the time of exploratory laparotomy, whereas non-CyA-treated ATX and euthymic controls had rejected the grafts. The CyA-treated ATX B10.MBR mice accepted donor-specific skin grafts, but rejected them following a challenge with third party B10.BR skin grafts. Untreated ATX and euthymic mice and 6 of 7 CyA-treated euthymic mice rejected donor skin within 15 days. Mixed lymphocyte reactions did not show an increased anti-donor response, but CML clearly showed sensitization and increased killing activity against donor-type targets in these mice. CONCLUSION: Allogeneic thymic transplantation across a class I MHC barrier under the cover of CyA induces a metastable state of tolerance in mice. To achieve this state, ATX of the recipient is required.

Animals↗
PubMed2001

Concomitant thymectomy and cardiac operation in a patient with pure red cell aplasia.

Pure red cell aplasia is a rare condition resulting in severe anemia. Medical therapy is indicated, unless a thymoma is present. In patients with concurrent cardiac pathology requiring operation, simultaneous operation should be contemplated to avoid risky resternotomy. We describe an exceptionally rare case of a patient with pure red cell aplasia secondary to a thymoma who underwent concomitant thymectomy and coronary artery grafting with a successful surgical outcome.

Combined Modality Therapy↗
PubMed2001

Video-assisted extended thymectomy in patients with thymoma by lifting the sternum.

We present use of minimally invasive video thoracoscopic surgery to perform complete extended thymectomy in patients with thymoma. These procedures were performed using a sternum-elevating method that provides a wide field of vision between the sternum and heart. Indications for this method are Masaoka Stage I, II and some Stage III (invasion to the lung and pericardium). This new method may be useful from the standpoint of minimal access, rapid recovery, less pain, and good cosmetic results.

Adult↗
PubMed1977

Transcervical thymectomy with the aid of mediastinoscopy for myasthenia gravis: eight years' experience.

Fifty-eight patients with myasthenia gravis, including 12 children, underwent thymectomy. Eleven of them (19%) had total stable remission and 42 (72%) showed clinical improvement and were able to reduce their anticholinesterase medication. These two groups combined comprised 53 patients (91%). There was no operative or postoperative mortality. Histopathological examination of the resected thymuses revealed a tumor (benign thymoma) in 4 patients (7%), thymitis in 36(62%), and no pathological changes in 18(31%). Patients with few or no germinal centers tended to achieve remission more rapidly than those with numerous germinal centers.

Adolescent↗
PubMed1989

Thymectomy for myasthenia gravis: recent observations and comparisons with past experience.

To our previous report on the results of thymectomy for myasthenia gravis in 249 patients operated on between 1954 and 1981, we add a current review of 84 patients treated between 1982 and 1987. All patients underwent a median sternotomy, although this was performed after a bilateral submammary skin incision in most of the 57 female patients. There were no operative deaths, but one late death occurred at 5 months. During a mean followup of 3.6 years, 67 patients (80%) benefited from operation with remission achieved in 30 (36%) and improvement noted in 37 (44%). Acetylcholine receptor site antibody was present in 43 patients, of whom 19 (44%) achieved remission in contrast to 9 (27%) of the 33 patients without antibody. Hyperplasia of the excised thymus in 38 patients was associated with remission in 20 (53%) in contrast to remission in 7 (20%) of the 35 patients whose glands were "normal" or atrophic. The best prognosis was found in the 23 patients who had both receptor site antibody and thymic hyperplasia, as remission occurred in 15 of them (65%) in contrast to only 6 (27%) of the 22 patients who had neither factor. Remission rates (remissions per 1,000 patient-months of follow-up) for the present series (84 patients), the previous group (249 patients), and the overall group (333 patients) are 9.95, 6.13, and 6.62, respectively.

Adult↗
PubMed1999

Long-term immunologic effects of thymectomy in patients with myasthenia gravis.

BACKGROUND: Thymectomy (Tx) is a common therapeutic option to treat myasthenia gravis (MG), but its effects on the immune system are still obscure in humans. OBJECTIVE: We sought to evaluate long-term immunologic effects of therapeutic Tx in patients with MG. METHODS: T- and B-cell subsets and T-cell repertoire were analyzed in 35 patients with MG, 16 with previous Tx (at least 8 years before), 6 with recent (<1 year) Tx, and 13 without Tx, as well as in 32 healthy subjects used as normal control subjects. Serum immunoglobulins and a variety of autoantibodies were also measured. A subsequent 3-year clinical follow-up was performed to verify the possible appearance of systemic autoimmune diseases. RESULTS: The long-term thymectomized (Txd) patients had mild T-cell lymphopenia and an expansion of some Vbeta families among circulating CD4+ and CD8+ T cells. They displayed a normal number of total B and CD5+ B-circulating lymphocytes, but they also displayed a polyclonal increase in serum IgM and IgG associated with the presence of high levels of a variety of organ- and nonorgan-specific autoantibodies, including anti-dsDNA and anticardiolipin, without clinical evidence of autoimmune disease. These serologic abnormalities were not detectable in both non-Txd and recently Txd patients. After 3 years, 2 long-term Txd patients had systemic lupus erythematosus and an undifferentiated connective tissue disease. CONCLUSIONS: The association between MG and laboratory findings of systemic autoimmune disease may be in part related to Tx rather than to MG. Tx may represent a risk for the development of systemic autoimmune disorders over years in patients with MG.

Adult↗
PubMed1999

Thymectomy in myasthenia gravis via video-assisted infra-mammary cosmetic incision.

We describe the technique, the benefits and the drawbacks of an original video-assisted thymectomy (VAT), performed through an inframammary cosmetic incision and median sternotomy in myasthenia gravis (MG) patients. This procedure is clinically valuable and cosmetically satisfactory so as to be very well accepted by patients, especially by young women. We report a review of 71 MG patients treated between 1993 and 1997. A clinical remission was obtained in 48 (80%) out of 60 patients who had been followed for at least 12 months from surgery. Fifty-three of these patients (93%) judged their cosmetic results to be excellent or good.

Esthetics↗
PubMed1999

Transcervical thymectomy.

Transcervical thymectomy is appropriate for managing carefully selected patients with myasthenia gravis due to its noninvasive nature, good cosmetic results, and favorable long-term outcomes. Contraindications to its use include the presence of a thymoma and advanced age. In optimally prepared patients, the operative complication rate is negligible and the average length of hospital stay is 1 to 2 days. The ultimate results of therapy often are not evident for several years postoperatively, indicating that comprehensive preoperative and postoperative treatment by a qualified neurologist is essential in optimizing outcomes. A meta-analysis of long-term results shows that 90% of patients who undergo the operation are improved, 80% become asymptomatic, and 50% achieve a complete remission.

Autoimmune Diseases↗
PubMed1981

The effect of plasmapheresis on post-thymectomy ocular dysfunction.

Five myasthenia patients with post-thymectomy residual ocular signs were treated with plasmapheresis. Despite a significant reduction in AChR antibody titer, there was no clinical improvement. Subsequently, there was a dramatic response to prednisone. The AChR antibody titer did not correlate with the clinical state of the individual patient. It is suggested that plasmapheresis may operate by removing a thymic factor and that prednisone acts by a different mechanism.

Adult↗
PubMed1980

Spontaneous remission of autoimmune encephalomyelitis is inhibited by splenectomy, thymectomy or ageing.

Experimental autoimmune encephalomyelitis (EAE) can be induced in genetically susceptible animals by injecting them with basic protein of myelin (BP) in a suitable adjuvant. EAE in adult Lewis rats is expressed clinically by acute paralysis and histologically by mononuclear cell infiltration of the central nervous system. Most rats spontaneously recover from EAE and show little or no damage to myelin. We report here that chronic progressive EAE with marked myelin lesions can be induced by a single injection of BP in complete Freund's adjuvant in intact 13-month old rats, or in 4-month old rats provided they have been splenectomized. Juvenile 2 1/2-month old rats recover spontaneously despite splenectomy. Thymectomy of young adult rats leads to relapsing EAE. These results illustrate that the clinical course of EAE is markedly influenced by age and integrity of immune organs. Furthermore, they provide an experimental model with features similar to those of chronic relapsing disease of the nervous system of man.

Aging↗
PubMed1975

Murine leukaemia virus expression in the AKR following thymectomy.

Thymectomy effectively prevents the development of spontaneous lymphoma in the AKR but how this effect is achieved remains to be determined. One possible mechanism, namely suppression of genomic expression of the oncogenic murine leukaemia virus now seems unlikely since levels of the group specific MuLV antigen were in comparision with their sham operated controls unaltered in both neonatally and adult thymectomized AKR.

Age Factors↗
PubMed1978

Effect of adult thymectomy on tumour immunity in mice.

The effect of adult thymectomy in DBA/2J mice on the in vitro response to syngeneic tumour cells was investigated. Spleen cells from adult mice which had been thymectomized 8 weeks previously demonstrated a severely impaired primary cytotoxic response to P815 tumour cells, whereas their cytotoxic responses to allogeneic cells (C57BL/6) and to non-H-2 antigens (BALB/c), and their ability to form a primary antibody response to sheep red blood cells was unimpaired. Suppressor T cells, specific for P815 cells, appeared early in the thymuses of animals inoculated with P815 cells (between 4 and 8 days after tumour-cell injection). No differences in tumour growth between animals thymectomized as adults and sham-operated controls were observed, and thymectomized tumour-bearing animals had levels of specific suppressor cells in their lymph nodes equivalent to the levels found in untreated controls. Severely thymocyte-deprived animals which had been thymectomized, irradiated and reconstituted with either marrow or spleen cells 8 weeks before tumour implantation succumbed more rapidly to metastatic tumour than did control animals.

Animals↗
PubMed1980

Human tumour xenografts established and serially transplanted in mice immunologically deprived by thymectomy, cytosine arabinoside and whole-body irradiation.

Mice immunologically deprived by thymectomy, cytosine arabinoside treatment and whole-body irradiation were used to study the growth of human tumours as xenografts. 10/16 melanoma biopsies, 4/13 ovarian carcinoma biopsies and 3/6 uterine cancer biopsies grew as serially transpllantable xenograft lines. The tumour lines were studied through serial passages by histology, histochemistry, electron microscopy, chromosome analysis, immune fluorescence, growth rate measurement and mitotic counts. They retained the characteristics of the tumours of origin, with the exception of loss of pigmentation in two melanomas, histological dedifferentiation in the uterine carcinomas, and increased mitotic frequency and growth rate in some melanomas. It was concluded that this type of animal preparation is as useful as alternative methods of immunological deprivation, or as athymic nude mice, for the growth of human tumour xenografts, at least for some experimental purposes.

Animals↗
PubMed1980

The effect of pre-natal thymectomy on lymphocyte sub-populations in the sheep.

Ten sheep foetuses were thymectomized between 55 and 77 days gestation. The subsequent growth of the lambs was not affected for periods up to 500 days after birth. Prior to 240 days of age the thymectomized lambs were markedly lymphopenic and the response of their blood lymphocytes to phytohaemagglutinin (PHA) was significantly reduced. Peanut agglutinin-binding cells were found to be depleted in the blood of thymectomized lambs, while an unmarked 'null' cell population was virtually absent. The absolute numbers of E-rosette forming cells and sIg+ cells were similar for both groups. These findings indicated that 'null' cells in sheep may be immature thymus-dependent lymphocytes. The effect of thymectomy on blood counts, PHA responsiveness and the numbers of 'null' cells were less evident in thymectomized sheep that survived beyond 240 days. Possible differentiation pathways for sheep T-cells are discussed, together with the role played by the thymus in the maturation of T-cells.

Animals↗
PubMed1999

Kinetics of T cell turnover following thymectomy.

We develop a mathematical formula that provides the number of cells in an isolated population that have divided k times in n days (O< or =k< or =n). This differential cell division formula is applied to the kinetics of peripheral T cells in the diabetes-prone BB rat following thymectomy. These rats received daily intraperitoneal injections of the DNA precursor, bromodeoxyuridine (BrdUrd), over a period of 12-13 days. As the cells divided, they incorporated BrdUrd progressively into their DNA molecules, and the differential formula provides a close prediction of the fraction of BrdUrd-positive T cells present each day during this 'pulse' phase. No further BrdUrd was administered after 13 days, and the diminishing fraction of BrdUrd-positive cells was recorded for several more weeks. The differential cell division formula was capable of describing the rather complex form of the retention curve as BrdUrd-tagged DNA molecules passed to progeny cells during this 'chase' phase. We believe that this simple formula may be found generally useful in describing cell kinetic data in mitotically active cells.

Animals↗
PubMed1996

Induction of autoimmune hepatitis and autoantibodies to liver antigens by neonatal thymectomy in mice.

We examined development of autoimmune hepatitis in neonatally thymectomized C3H/HeN mice and tried to characterize the nature of liver antigens recognized by the autoantibodies at the molecular level. Autoantibodies to crude liver proteins detected by ELISA were found in 12(67%) of 18 mice thymectomized 2 days after birth. However, autoantibodies were not detected in mice thymectomized 7 days after birth. The autoantibodies mainly consisted of IgG and reached the maximum level 8 weeks after birth. Hepatic inflammation, mononuclear cell infiltration in the portal area, was seen in 5 (28%) of 18 mice thymectomized 2 days after birth, but not in mice thymectomized 7 days after birth. Most infiltrating cells were Thy-1+ lymphocytes. The serum autoantibody level to crude liver proteins in mice with hepatitis was much higher than that in mice without hepatitis. We fractionated crude liver proteins by a Sepharose 6B column and examined the reactivity against the autoantibodies. The autoantibodies of three of five mice with hepatitis reacted with th approximately 150kD liver proteins other than liver-specific protein (LSP). By Western immunoblotting of SCS-PAGE using LSP and fractionated liver proteins, we found that the molecular weights of the target antigens were 52kD in LSP and 150kD (strong band), 138, 128, 120 and 110kD (weak band) in fractionated liver proteins other than LSP. This 150-kD target molecule in crude liver proteins was found only in liver. These results indicate that hepatitis and autoantibodies to liver proteins are induced spontaneously by neonatal thymectomy in mice, and the candidates of autoantigen in this hepatitis model are 52-kD protein in LSP and 150-kD liver proteins different from LSP. Still more, we regard the 150-kD molecule as a new autoantigen related to hepatitis.

Age Factors↗
PubMed1996

Late-term fetal thymectomy does not prevent the development of gut-homing T cells after birth.

Tissue-specific circulation of T cells is a critical element in the integration of systemic immune responses. Current models of T-cell migration suggest that homing specificities of T cells for tissues such as gut and skin are generated outside the thymus as a result of activation of virgin T cells by antigen in lymph nodes. We have used the sheep fetus (which is immunologically virgin and contains no memory or effector T-cell subsets) to examine the migration of 51Cr-labelled T cells in vivo. We report that gut-homing T cells are not present in the fetus and that gut-homing T cells from postnatal lambs home normally to fetal gut. Fetal thymectomy performed immediately prior to birth failed to prevent the development of gut-homing T cells in postnatal life. Gut-homing specificities on T cells are thus acquired extrathymically.

Animals↗