Blockade of Leukocyte Function Antigen-1 (LFA-1) in Clinical Islet Transplantation

Fotino, Carmen; Pileggi, Antonello

doi:10.1007/s11892-011-0214-y

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…Leukocyte function antigen-1 (LFA-1) is a cell surface adhesion molecule expressed on a variety of leukocytes that controls leukocyte transmigration from blood to peripheral tissues 190 . In T cells, LFA-1 is also essential for the establishment of an immunologic synapse between T cells and APCs.…”

Section: Impact Of Alternative Immunosuppressive Agents On Tregmentioning

confidence: 99%

Impact of Immune-Modulatory Drugs on Regulatory T Cell

2016

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Immunosuppression strategies that selectively inhibit effector T cells while preserving and even enhancing CD4+FOXP3+ regulatory T cells (Treg) permit immune self-regulation and may allow minimization of immunosuppression and associated toxicities. Many immunosuppressive drugs were developed before the identity and function of Treg were appreciated. A good understanding of the interactions between Treg and immunosuppressive agents will be valuable to the effective design of more tolerable immunosuppression regimens. This review will discuss preclinical and clinical evidence regarding the influence of current and emerging immunosuppressive drugs on Treg homeostasis, stability, and function as a guideline for the selection and development of Treg-friendly immunosuppressive regimens.

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Section: Impact Of Alternative Immunosuppressive Agents On Tregmentioning

confidence: 99%

Impact of Immune-Modulatory Drugs on Regulatory T Cell

2016

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“…Induction therapy with anti-CD52 antibody/alemtuzumab (e.g., Campath) has been reported with encouraging longterm function 122 . Biologic agents such as agents targeting co-stimulation pathways in immune cells and adhesion molecules (CTLA4-Ig, LFA-1 PD-1/PD-L1 CD40) and chemokine receptors (CXCR1/2) that potentially lower islet cell and organ toxicity profiles are being evaluated and shows promising results [123][124][125][126] .…”

Section: Immunosuppressive Protocols In Islet Transplantationmentioning

confidence: 99%

Anakinra and Tocilizumab Enhance Survival and Function of Human Islets during Culture: Implications for Clinical Islet Transplantation

et al. 2014

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Pretreatment culture before islet transplantation represents a window of opportunity to ameliorate the proinflammatory profile expressed by human b-cells in duress. Anakinra (IL-1 receptor antagonist) and tocilizumab (monoclonal IL-6 receptor antibody) are two known anti-inflammatory agents successfully used in the treatment of inflammatory states like rheumatoid arthritis. Both compounds have also been shown to reduce blood glucose and glycosylated hemoglobin in diabetic patients. We therefore sought to evaluate the impact of anakinra and tocilizumab on human b-cells. The islets were precultured with or without anakinra or tocilizumab and then transplanted in a marginal mass model using human islets in immunodeficient mice. Islet viability was evaluated in an in vitro model. The pretreatment culture led to a significantly improved engraftment in treated islets compared to the vehicle. Anakinra and tocilizumab are not toxic to human islets and significantly reduce markers of inflammation and cell death. These results strongly support a pretreatment culture with anakinra and tocilizumab prior to human islet transplantation.

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