The thymus is a vital primary lymphoid organ that provides unique microenvironments for the proliferation, differentiation, and maturation of T cells. With advancing age, however, the thymus gradually undergoes age-related involution and reduction in immune function, which are characterized by decreases in tissue size, cellularity, and naïve T cell output. This dynamic process leads to the reduced efficacy of the immune system with age and contributes to the increased susceptibility to infection, autoimmune disease, and cancer. In addition, bone marrow transplantation, radio-chemotherapy and virus infection also impair the thymus and give rise to the decline in immune function. Therefore, understanding the molecular mechanisms involved in age-related thymic involution and development of novel therapeutic strategies for thymic rejuvenation have gained considerable interests in recent years. This review emphasizes thymic microenvironments and thymocyte-stromal cell interactions and summarizes our current knowledge about thymic rejuvenation in terms of sex steroid, cytokines, growth factors, hormones, transcription factors, cell graft, and microRNAs. At the end of each discussion, we also highlight unanswered issues and describe possible future research directions.
Aging ; Cell Differentiation ; Cytokines ; Gonadal Steroid Hormones ; Hormones ; Humans ; Intercellular Signaling Peptides and Proteins ; Rejuvenation ; Stromal Cells ; T-Lymphocytes ; Thymus Gland

Thymic hyperplasia is frequently observed in Graves' disease. However, detectable massive enlargement of the thymus is rare, and the mechanism of its formation has remained elusive. This case showed dynamic changes in thymic hyperplasia on serial computed tomography images consistent with changes in serum thyrotropin receptor (TSH-R) antibodies and thyroid hormone levels. Furthermore, the patient's thymic tissues underwent immunohistochemical staining for TSH-R, which demonstrated the presence of thymic TSH-R. The correlation between serum TSH-R antibody levels and thymic hyperplasia sizes and the presence of TSH-R in her thymus suggest that TSH-R antibodies could have a pathogenic role in thymic hyperplasia.
Adult ; Female ; Graves Disease/*complications/surgery/therapy ; Humans ; Male ; Receptors, Thyrotropin/blood ; Thymus Gland/diagnostic imaging ; Thymus Hyperplasia/*diagnostic imaging/etiology/immunology ; Thyroid Hormones ; Thyroidectomy ; Thyrotropin/blood ; Tomography, X-Ray Computed ; Young Adult

Drug Therapy, Combination ; Follow-Up Studies ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; administration & dosage ; Thymus Hormones ; administration & dosage ; Vidarabine Phosphate ; administration & dosage

Aging ; physiology ; Animals ; Catalase ; metabolism ; Circadian Rhythm ; Free Radicals ; metabolism ; Lipid Peroxides ; metabolism ; Male ; Melatonin ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Thymus Hormones ; pharmacology

BACKGROUND: In the thymus, developing thymocytes continually interact with thymic epithelial cell components. Self MHC restriction of mature T cells are imposed in the thymus through interaction of immature double positive thymocytes and thymic cortical epithelial cells. The site of negative selection, however, is a matter of debate. Through systemic injection of anti-TCR antibody or antigenic peptides, investigators suggested that most of the negative selection occurs in the thymic cortex. But the requirements for negative selection, i.e cellular counterparts and costimulatory molecules are more available in the medulla or cortico-medullary junction rather than in the thymic cortex. METHODS: The direct and indirect pathways of thymocyte death after systemic anti-TCR antibody injection were separated through several experimental systems. B6 mice were either adrenalectomized or sham-adrenalectomized to evaluate the role of endogenous glucocorticoids from adrenal gland. Role of TNF were evaluated through using TNF receptor double knockout mice. RESULTS: We found that without indirectly acting mediators such as TNF-alpha or corticosteroid, double positive thymocyte death were minimal by systemic injection of anti-TCR antibody in TNF receptor double knockout neonatal mice. Also by analyzing neonatal wild-type mice with adoptively transferred mature T cells, only peripheral activation of mature T cells could induce extensive double positive thymocyte death. CONCLUSION: Thus, systemically injected anti-TCR antibody mediated thymocyte death are mostly induced through indirect pathway.
Adrenal Cortex Hormones* ; Adrenal Glands ; Animals ; Epithelial Cells ; Glucocorticoids ; Humans ; Mice ; Mice, Knockout ; Peptides ; Receptors, Tumor Necrosis Factor ; Research Personnel ; T-Lymphocytes ; Thymocytes* ; Thymus Gland ; Tumor Necrosis Factor-alpha

BACKGROUND: Thymopentin(TP-5) is an immunomodulatory agent which may be a promising new drug in the treatment of patients with severe atopic dermatitis. OBJECTIVE: The aim of this study was to evaluate the efficacy of thymopentin for treatment of severe atopic dermatitis. MATERIAL AND METHOD: Fifteen patients with severe atopic dermatitis received subcutaneous injections of 50mg thymopentin three times per week for 6 weeks. Clinical extent and severity parameters were assessed at baseline, at regular intervals during therapy and 4 weeks posttherapy. Use of antihistamine and topical steroid were permitted. RESULT: Significant reduction in severity scores and body surface area involvement was observed and no significant side effects were noted(p<0.05). CONCLUSION: Thymopentin may be considered to be an effective adjunctive therapeutic agent in the treatment of severe atopic dermatitis. Further studies will be needed to determine the action mechanism of thymopentin.
Body Surface Area ; Dermatitis, Atopic* ; Humans ; Injections, Subcutaneous ; Thymopentin*

The aim of this study is to evaluate the therapeutic potential of the immunostimulating adjuvant in patients with HCCs¬¬¬.46 patients with HCCs were divided into 2 groups: group I (30pts) treated by Transcatheter Oily Chemoembolization (TOCE alone), group II resulted in a better clinical improvement, decreased AFP and tumor size, and a longer mean survival time versus group I. Combined treatment demonstrated a significant increase in lymphocytes expressing CD 16-CD 56 with NK activity and followed by a rise in lymphocyte with morphological feature of cytotoxic lymphocyte ( CD8 positive) was observed
Liver Neoplasms ; Thymosin ; Therapeutics

The aim of this study is to evaluate the therapeutic potential of the immunostimulating adjuvant in patients with HCCs¬¬¬.46 patients with HCCs were divided into 2 groups: group I (30pts) treated by Transcatheter Oily Chemoembolization (TOCE alone), group II resulted in a better clinical improvement, decreased AFP and tumor size, and a longer mean survival time versus group I. Combined treatment demonstrated a significant increase in lymphocytes expressing CD 16-CD 56 with NK activity and followed by a rise in lymphocyte with morphological feature of cytotoxic lymphocyte ( CD8 positive) was observed
Liver Neoplasms ; Thymosin ; Therapeutics

The Job syndrome is a primary immunodeficiency disorder characterized by markedly elevated serum IgE levels, recurrent severe infections of the skin and sinoplmonary tract, including staphylococcal pneumonias, chronic eczematoid dermatitis, coarse facial features, and mild eosinophilia. In 1966, Davis et al discribed two patients with severe eczema, chroic sinopulmonary infections, and recurrent staphylococcal abscesses originally. The reason for immunocompromise in the Job syndrome remains unclear, but a chemotactic defect in neutrophils has been described. We have experienced a case of Job syndrome in a 9-year-old girl who had suffered from severe recurrent multiple infections since 2 month of age. After treatment with thymopentin, she was improved clinically. A brief review of related literature is presented.
Abscess ; Child ; Dermatitis ; Eczema ; Eosinophilia ; Female ; Humans ; Immunoglobulin E ; Job Syndrome ; Neutrophils ; Pneumonia, Staphylococcal ; Skin ; Thymopentin*

PURPOSE: Atopic dermatitis is a chronic relapsing inflammatory skin disease that results from allergic reaction. Steroid therapy has become a major therapeutic modality for treatment of atopic dermatitis. Several immunomodulatory therapies have been tried for atopic dermatitis. In this study thymopentin therapy was performed and its clinical effects and laboratory results were evaluated. METHODS: Atopic dermatitis with typical clinical symptoms were included in this study. Twelve patients were treated with subcutaneous injection of thymopentin ( (Imupentin ) at a dose of 1 mg/kg, three times per week for eight weeks. Clinical scores were measured by Hanifin scoring system before and at the end of the treatment. General hematologic laboratory tests such as hemoglobin, hematocrit, WBC count, neutrophil percentage, lymphocytes percentage and eosinophil percentage as well as blood IgE level were conducted at the same time. RESULTS: The clinical severity of atopic dermatitis patients was markedly improved by thymopentin therapy. The clinical severity score improved by 85.5%. Three patients showed complete remission of clinical status at the end of thymopentin therapy. Hemoglobin, hematocrit, WBC counts, neutrophil percentage, and lymphocyte percentage were not affected by the thymopentin therapy. Eosinophil percentage and blood IgE level were significantly reduced statistically. CONCLUSION: Thymopentin therapy is an effective immunomodulatory therapeutic modality in atopic dermatitis. Thymopentin decreased eosinophil percentage and blood IgE levels without other hematologic changes.
Dermatitis, Atopic* ; Eosinophils ; Hematocrit ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunomodulation ; Injections, Subcutaneous ; Lymphocytes ; Neutrophils ; Skin Diseases ; Thymopentin*