title: 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.affiliation: Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Electronic address: naresh_pgi@hotmail.com.
authors.forename: Naresh
authors.initials: N
authors.lastname: Sachdeva
authors.affiliation: Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Mahinder
authors.initials: M
authors.lastname: Paul
authors.affiliation: Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Darshan
authors.initials: D
authors.lastname: Badal
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Neenu
authors.initials: N
authors.lastname: Jacob
authors.affiliation: Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Devi
authors.initials: D
authors.lastname: Dayal
authors.affiliation: Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Arora
authors.affiliation: Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Sanjay Kumar
authors.initials: SK
authors.lastname: Bhadada
mesh_terms: D000328:Adult; D058070:Asymptomatic Diseases; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D011498:Protein Precursors / Q000378:metabolism*
chemical_list: D007328:Insulin; D011498:Protein Precursors; C013737:preproinsulin
keywords: CD8+ T cells; Dextramers; Latent autoimmune diabetes in adults; Preproinsulin; Type 1 diabetes