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T regulatory cell mediated immunotherapy for solid organ transplantation: A clinical perspective.

ABSTRACT: T regulatory cells (Tregs) play a vital role in suppressing heightened immune responses, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which make them a potential candidate for cell-based immunotherapy to suppress uncontrolled activation of graft specific inflammatory cells and their toxic mediators. These grafts specific inflammatory cells (T effector cells) and other inflammatory mediators (Immunoglobulins, active complement mediators) are mainly responsible for graft vascular deterioration followed by acute/chronic rejection. Treg mediated immunotherapy is under investigation to induce allospecific tolerance in various ongoing clinical trials in organ transplant recipients. Treg immunotherapy is showing promising results but the key issues regarding Treg immunotherapy are not yet fully resolved including their mechanism of action, and specific Treg cell phenotype responsible for a state of tolerance. This review highlights the involvement of various subsets of Tregs during immune suppression, novelty of Tregs functions, effects on angiogenesis, emerging technologies for effective Treg expansion, plasticity and safety associated with clinical applications. Altogether this information will assist in designing single/combined Treg mediated therapies for successful clinical trials in solid organ transplantations.

SUBMITTER: Khan MA

PROVIDER: S-EPMC5319206 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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T regulatory cell mediated immunotherapy for solid organ transplantation: A clinical perspective.

Khan Mohammad Afzal MA

Molecular medicine (Cambridge, Mass.) 20161122

T regulatory cells (Tregs) play a vital role in suppressing heightened immune responses, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which make them a potential candidate for cell-based immunotherapy to suppress uncontrolled activation of graft specific inflammatory cells and their toxic mediators. These grafts specific inflammatory cells (T effector cells) and other inflammatory mediators (Immunoglobulins, active complement mediators ...[more]

PMID: 27878210

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Project description:BackgroundThe number of Medicaid beneficiaries has increased under the Affordable Care Act, improving access to solid organ transplantation in this disadvantaged patient cohort. It is unclear what impact Medicaid expansion will have on transplantation outcomes. We performed a retrospective cohort analysis to measure the frequency and variation in Medicaid transplantation and post-transplantation survival in Medicaid patients.Study designAdult heart, lung, liver, and renal transplant recipients between 2002 and 2011 (n = 169,194) reported to the Scientific Registry of Transplant Recipients were identified. Transplant recipients were classified based on insurance status (private, Medicare or Medicaid). Outcomes measures included 5-year post-transplantation survival, summarized using Kaplan-Meier curves and compared with log-rank tests. Organ-specific Cox proportional hazards models were used to adjust for donor and recipient factors.ResultsMedicaid patients comprised 8.6% of all organ transplant recipients. Fewer transplantations were performed than expected among Medicaid beneficiaries for all organs except liver (liver: observed to expected ratio = 1.21; 95% CI, 0.68-1.90; heart: observed to expected ratio = 0.89; 95% CI, 0.44-1.49; lung: observed to expected ratio = 0.57; 95% CI, 0.22-1.06; renal: observed to expected ratio = 0.32; 95% CI, 0.08-0.72). Medicaid transplant recipients were listed with more severe organ failure and experienced shorter transplant wait times. Post-transplantation survival was lower in Medicaid patients compared with private insurance for all organs. Post-transplantation survival in Medicaid patients was similar to Medicare patients for heart, liver, and renal but lower in lung.ConclusionsMedicaid organ transplant beneficiaries had significantly lower survival compared with privately insured beneficiaries. The more severe organ failure among Medicaid beneficiaries at the time of listing, suggested a pattern of late referral, which might account for worse outcomes. Implementation of the Affordable Care Act gives the opportunity to develop the necessary infrastructure to ensure timely transplantation referrals and improve long-term outcomes in this vulnerable population.

Dataset Information

T regulatory cell mediated immunotherapy for solid organ transplantation: A clinical perspective.

Publications

T regulatory cell mediated immunotherapy for solid organ transplantation: A clinical perspective.

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