Improvement of T cell mediated immunity

A cell and cell group technology, which can be used in medical preparations containing active ingredients, endocrine system diseases, peptide/protein components, etc., and can solve problems such as memory cell deviation

Inactive Publication Date: 2008-03-26
NORWOOD IMMUNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This is further exemplified by the recent work of Timm and Thoman (1999), who showed that although aged mice post-BMT CD4 + T cells regenerate, but they exhibit a bias toward memory cells due to an aging peripheral microenvironment and poor thymic production of naive T cells

Method used

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  • Improvement of T cell mediated immunity
  • Improvement of T cell mediated immunity
  • Improvement of T cell mediated immunity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] Example 1: Reversion of age-induced thymic atrophy

[0074] Materials and Methods

[0075] animal

[0076] CBA / CAH and C57B16 / J male mice were obtained from CentralAnimal Services, Monash University, and housed under conventional conditions. Ages range from 4-6 weeks to 26 months and are indicated where relevant.

[0077] castration

[0078] By intraperitoneal injection of 0.3 mL of 0.3 mg xylazine (Xylazine; BayerAustralia Ltd., Botany, New South Wales, Australia) and 1.5 mg of ketamine hydrochloride (Cordamine; Parke-Davis, Caringbah, New South Wales, Australia) Anesthetize the animal with a solution in saline. Surgical castration is performed by incision of the scrotum to expose the testes, which are ligated with sutures and then removed along with the surrounding fatty tissue.

[0079] Bromodeoxyuridine (BrdU) introduction

[0080] Mice received two intraperitoneal injections (100 mg / kg body weight in 100 microliters of PBS) of BrdU (Sigma Chemical Co., St. Lo...

Embodiment 2

[0125] Example 2: Reversal of Chemotherapy or Radiation Induced Thymic Atrophy

[0126] Following radiation or cyclophosphamide treatment, the rate of thymus regeneration was significantly increased in castrated mice (one week before or on the day of treatment).

[0127] In the thymus, the structure of the irradiated mouse thymus was severely disrupted, accompanied by a decrease in rapidly dividing cells. Cortical collapse, reminiscent of aged / hydrocortisone treated thymus showing loss of DN and DP thymocytes. αβ-TCR expression on CD4+ and CD8+ SP thymocytes with evidence of downregulation-apoptotic cells. In comparison, cyclophosphamide-treated animals showed less severe disruption of thymus architecture and faster regeneration rates of DN and DP thymocytes.

[0128] By 1 week post-treatment, even at this earlier stage, castrated mice exhibited significant thymus regeneration (Figures 6, 7 and 8). In comparison, non-castrated mice exhibit a severe loss of DN and DP thymocy...

Embodiment 3

[0131] Example 3: Thymus regeneration following sex steroid suppression leads to restoration of deficient peripheral T cell function

[0132] To determine whether castration can enhance the immune response, herpes simplex virus (HSV) immunity was tested, as it allows the study of disease progression and the role of CTL (cytotoxic) T cells. Castrated mice had qualitatively and quantitatively improved reactivity to the virus. Mouse footpads were immunized and popliteal (draining) lymph nodes were analyzed on day 5 post immunization. Additionally, footpads were taken and homogenized to determine virus titers at specific times throughout the assay.

[0133] On day 5 after immunization, castrated mice had significantly larger lymph node cellularity than aged mice (Figure 10). In addition, the number of activated cells in lymph nodes was significantly increased compared to aged controls (Figures 10 and 11). Further, the number of activated cells correlated with that found in juve...

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Abstract

The present invention provides a method of modifying the T-cell population makeup or increasing the number of T-cells in a subject having depressed or abnormal T-cell population or function, the method comprising disrupting sex steroid signalling to the thymus in the subject. The invention can be used to treat a subject suffering from a wide array of diseases, for example, cancer, HIV infection, autoimmunity and hypersensitivity. In addition, the present invention provides methods for enhancing an immune response to an antigen, treating an autoimmune disease, and decreasing a host-vs-graft reaction in a transplantation donor.

Description

field of invention [0001] The present invention relates to methods of altering the composition or increasing the number of T cell populations in patients with suppressed or abnormal T cell populations or functions. These methods include disrupting the patient's sex steroid signaling to the thymus. Background of the invention [0002] The thymus is largely influenced by its two-way communication with the neuroendocrine system (Kendall, 1988). Of particular importance is the interaction between the pituitary, adrenal, and gonads on thymic function, both trophic (TSH and GH) and atrophic (LH, FSH, and ACTH) (Kendall, 1988; Homo-Delarche, 1991). Indeed, one of the characteristic features of thymus physiology is a progressive decline in structure and function, which matches the increase in circulating sex steroid production during adolescence (Hirokawa and Makinodan, 1975; Tosi et al., 1982 and Hirokawa et al., 1994). The precise targets of the hormones and the mechanism by whi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/09A61P37/06A61P37/04A61P5/02A61P5/24A61K31/167A61K31/445A61K38/00A61K38/04A61K39/00A61K39/39A61K45/00A61P15/00A61P31/18A61P35/00
CPCA61K38/09A61K39/39A61P15/00A61P31/18A61P35/00A61P37/04A61P37/06A61P5/02A61P5/24A61K38/00
Inventor 理查德·伦诺克斯·博伊德
Owner NORWOOD IMMUNOLOGY
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