Apoptotic T Cell Induction for Autoimmune Tolerance
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Solution Overview
Problem
Current therapies for autoimmune diseases face challenges in inducing antigen-specific regulatory T cells that can effectively target inflammatory immune cells without compromising the overall immune response, particularly in patients with established autoimmune diseases where the immune system is dysregulated.
Innovation Solution
A method involving the administration of anti-CD4 and/or anti-CD8 antibodies to induce apoptosis in T cells, combined with low-dose irradiation and the use of autoantigen-specific peptides to reprogram the immune system, creating an immunoregulatory milieu that generates antigen-specific Treg cells, thereby restoring tolerance to self-antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Treg cells are induced in naïve mice before disease establishment, then immune tolerance is maintained, but the Treg cells lose suppressive activity or convert to effector cells in the dysregulated inflammatory state of established autoimmune disease
Solution Approach 1:
The patent applies preliminary action by inducing apoptosis and creating an immunoregulatory milieu before administering the autoantigen. This sequence prepares the immune environment in advance to ensure that Treg cells will be properly induced and maintain their suppressive function, rather than converting to effector cells. The apoptosis induction and immunoregulatory milieu creation occur prior to antigen exposure, setting the stage for successful tolerance induction.
Solution Approach 2:
The patent changes key parameters of the immune environment by inducing apoptosis and creating an immunoregulatory milieu. This involves altering the cytokine profile, cell population dynamics, and inflammatory state to create conditions favorable for Treg cell induction and maintenance. By changing these environmental parameters, the patent ensures Treg cells remain suppressive rather than converting to effector cells.
2Reliability
If anti-CD4 and anti-CD8 antibodies are administered to induce T cell apoptosis, then an immunoregulatory milieu is created, but the overall immune response may be compromised
Solution Approach 1:
The patent uses partial action by administering antibodies that deplete only specific T cell subsets (CD4+ and/or CD8+) rather than causing complete immune suppression. This selective depletion is sufficient to create the necessary immunoregulatory milieu for Treg induction while preserving other immune functions. The action is calibrated to achieve the minimum necessary effect without excessive immunosuppression.
Solution Approach 2:
The patent uses apoptotic T cells as an intermediary to create the immunoregulatory milieu. Rather than directly suppressing the immune response, the depleting antibodies induce apoptosis, and the apoptotic cells themselves serve as mediators that release signals and create the regulatory environment necessary for Treg induction. This intermediary mechanism allows immune modulation without direct suppression.
3Reliability
If autoantigen-specific peptides are administered alone, then antigen presentation occurs, but long-term immune tolerance cannot be established without the immunoregulatory milieu
Solution Approach 1:
The patent applies preliminary action by creating the immunoregulatory milieu through apoptosis induction before administering the autoantigen. This preparatory step ensures that when the antigen is presented, the immune system is in the correct state to establish long-term tolerance rather than mounting a conventional immune response. The preliminary creation of the regulatory environment is essential for sustained tolerance.
Solution Approach 2:
The patent ensures continuity of useful action by establishing a self-sustaining immunoregulatory system. The initial apoptosis induction creates conditions for Treg induction, and these newly induced Treg cells continue to maintain tolerance long-term without requiring repeated antigen administration or continued antibody treatment. The useful action of immune regulation becomes continuous and self-maintaining.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively suppresses autoimmune responses in target tissues without compromising the overall immune response, demonstrating therapeutic potential for autoimmune diseases like multiple sclerosis and type 1 diabetes by inducing long-term immune tolerance.
Implementation Method 1
administering an effective amount of an anti-CD4 antibody, anti-CD8 antibody, or both to the subject to induce apoptosis in T cells
Implementation Method 2
administering an effective amount of low-dose irradiation to the subject suffering from the autoimmune disease or disorder to induce apoptotic cells
Data Source
AI summary
The disclosure provides methods of tolerizing or treating a subject suffering from an autoimmune or autoinflammatory disease or disorder to an antigen associated with the autoimmune disease or disorder. The disclosure also features kits for carrying out the methods.