Immune interventions in type 1 diabetes: blocking progression towards uncontrollable autoimmunity

PERONE, MJ

Simposio; First French-Argentine Immunology Congress (FAIC). Autoimmunity and Immunotherapy Symposium; 2010

<!-- /* Font Definitions */ @font-face {font-family:Arial; panose-1:2 11 6 4 2 2 2 2 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:3 0 0 0 1 0;} @font-face {font-family:Cambria; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin-top:0cm; margin-right:0cm; margin-bottom:10.0pt; margin-left:0cm; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Cambria; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} @page Section1 {size:612.0pt 792.0pt; margin:72.0pt 90.0pt 72.0pt 90.0pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Most of the diagnosed type 1 diabetes patients have the immune-mediated disease (T1AD) involving chronic and progressive T cell-mediated specific b-cell mass destruction. T1AD is multifactorial in origin with both genetically and environmental determinants conferring susceptibility to disease onset. Prevention of uncontrollable autoimmunity in therapies for T1AD is mandatory to preserve b-cells mass. Therefore, immunomodulatory strategies directed to inhibiting the activity of self-reactive T cell clones as well as induction of regulatory T cells would be beneficial for prevention of T1AD or recurrence of b-cells autoimmunity against islet cell allograft. The discovery of agents with potential to down-regulate inflammation and/or induce apoptosis of activated b-cell self-reactive T cell clones is warranted. Agents that fulfill these qualities have potential for therapeutic use, and might induce tolerance in autoimmune diabetes and islet transplantation. We have recently described strong experimental evidence of the employment of galectin-1, a soluble lectin, able to restore immune balance in T1AD mouse models by means of different mechanisms. Following a similar rationale we are now searching for novel compounds and combinatorial therapies without unacceptable risks associated with continuous immune suppression to control the autoimmune burden of T1AD and hopefully, reaching permanent arrest of autoimmunity. Achieving even a residual b-cell mass preservation and therefore, improving metabolic parameters will delay life-threatening complications.