Less Is More: The Detrimental Consequences of Immunosuppressive Therapy in the Treatment of Type-1 D

[h=1]http://www.ncbi.nlm.nih.gov/pubmed/25793647[/h]

• Abstract

Int Rev Immunol. 2015 Mar 20. [Epub ahead of print]
[h=1]Less Is More: The Detrimental Consequences of Immunosuppressive Therapy in the Treatment of Type-1 Diabetes.[/h]Askenasy N1.
[h=3]Author information[/h]

[h=3]Abstract[/h]The prevalent current approach to type 1 diabetes (T1D) is the abrogation of pathogenic potential by immunosuppressive therapy, an intuitive approach aiming to slow down disease progression by the reduction of pathogenic burden. In spite of promising initial results in rodent models, there has been little efficacy of most lymphoreductive strategies in human subjects. Our analysis suggests that lymphopenia is the common denominator of ineffective immunosuppressive therapies: Immune rebound from lymphopenia is associated per se with increased susceptibility to immune reactivity, including relapse of autoimmunity. In addition, immune homeostasis and self-tolerance are not restored. These considerations raise the following question: What is the allowed degree of immunosuppressive therapy that does not elicit recurrent autoimmunity. More effective therapeutic strategies include targeted deletion of pathogenic cells, preferably in the pancreatic islets and regional lymphatics using selective T cell activation markers, re-education and remodeling of effector responses.


[h=4]KEYWORDS:[/h]T cell depletion; immunomodulation; immunosuppressive therapy; lymphopenia; type 1 diabetes