Preproinsulin specific CD8+ T cells in subjects with latent autoimmune diabetes show lower frequency and different pathophysiological characteristics than those with type 1 diabetes.

Abstract

Latent autoimmune diabetes in adults (LADA) resembles type 1 diabetes (T1D) in disease presentation except that its onset is slow. We compared pathophysiological characteristics of CD8+ T cells recognizing preproinsulin (PPI) derived epitopes in both disease groups using MHC-I dextramers (DMRs) in peripheral blood and after in-vitro stimulation with PPI. Subjects with T1D harbored higher frequency of DMR+ CD8+ T cells with relatively higher frequency of effector T cell subsets. Following stimulation with PPI, an increase in DMR+ CD8+ T cells, particularly the central-memory subset was observed in T1D group, whereas no significant change in DMR+ CD8+ T cell subsets was observed in LADA group. Intracellular expression of Granzyme-B and Perforin in DMR+ CD8+ T cells was comparable in both the groups. In conclusion, lower frequency and inferior proliferative potential on account of a relatively restrained central-memory subset of PPI specific CD8+ T cells are associated with slow rate of disease progression in LADA.

• Authors: Naresh Sachdeva, Mahinder Paul, Darshan Badal, Rajendra Kumar, Neenu Jacob, Devi Dayal, Anil Bhansali, Sunil Kumar Arora, Sanjay Kumar Bhadada
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 157 Issue 1 Pg. 78-90 (Mar 2015) ISSN: 1521-7035 [Electronic] United States
• PMID: 25597827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Insulin
• Protein Precursors
• preproinsulin

Topics

• Adult
• Asymptomatic Diseases
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Child
• Diabetes Mellitus, Type 1 (immunology, physiopathology)
• Female
• Humans
• Insulin (metabolism)
• Male
• Protein Precursors (metabolism)