title: Targeting memory T cells in type 1 diabetes.
abstract: Type 1 diabetes (T1D) is a chronic autoimmune disease that leads to progressive destruction of pancreatic beta cells. Compared to healthy controls, a characteristic feature of patients with T1D is the presence of self-reactive T cells with a memory phenotype. These autoreactive memory T cells in both the CD4(+) and CD8(+) compartments are likely to be long-lived, strongly responsive to antigenic stimulation with less dependence on costimulation for activation and clonal expansion, and comparatively resistant to suppression by regulatory T cells (Tregs) or downregulation by immune-modulating agents. Persistence of autoreactive memory T cells likely contributes to the difficulty in preventing disease progression in new-onset T1D and maintaining allogeneic islet transplants by regular immunosuppressive regimens. The majority of immune interventions that have demonstrated some success in preserving beta cell function in the new-onset period have been shown to deplete or modulate memory T cells. Based on these and other considerations, preservation of residual beta cells early after diagnosis or restoration of beta cell mass by use of stem cell or transplantation technology will require a successful strategy to control the autoreactive memory T cell compartment, which could include depletion, inhibition of homeostatic cytokines, induction of hyporesponsiveness, or a combination of these approaches.
authors.affiliation: Clinical Trials Group, Immune Tolerance Network, 185 Berry Street, Suite 3515, San Francisco, CA, 94107, USA. mehlers@immunetolerance.org.
authors.forename: Mario R
authors.initials: MR
authors.lastname: Ehlers
authors.affiliation: Translational Medicine, Immunology Development, Janssen R&D, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA, 19477, USA. mrigby@ITS.JNJ.com.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Rigby
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: Alefacept; Autoimmunity; CD2; CD3; Central memory T cells; Costimulation blockade; Effector memory T cells; Homeostatic cytokines