title: CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes.
abstract: Previous cross-sectional analyses demonstrated that CD8(+) and CD4(+) T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4(+) T-cell cytokine production and autoreactive CD8(+) T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4(+) T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8(+) T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4(+) T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8(+) T-cells and more rapid beta-cell loss. In conclusion, CD4(+) T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8(+) T-cells are unique to T1D. Thus, autoreactive CD8(+) cells may serve as a more T1D-specific biomarker.
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Ghanashyam
authors.initials: G
authors.lastname: Sarikonda
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; University of California San Diego, San Diego, CA, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pettus
authors.affiliation: University of California San Diego, San Diego, CA, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Phatak
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Sowbarnika
authors.initials: S
authors.lastname: Sachithanantham
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Miller
authors.affiliation: Novo Nordisk Type 1 Diabetes R & D Center, Seattle, WA, USA.
authors.forename: Johnna D
authors.initials: JD
authors.lastname: Wesley
authors.affiliation: Ayasdi, Inc., Palo Alto, CA, USA.
authors.forename: Eithon
authors.initials: E
authors.lastname: Cadag
authors.affiliation: University of California San Diego, San Diego, CA, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Chae
authors.affiliation: University of California San Diego, San Diego, CA, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ganesan
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Ronna
authors.initials: R
authors.lastname: Mallios
authors.affiliation: University of California San Diego, San Diego, CA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Edelman
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; Novo Nordisk Type 1 Diabetes R & D Center, Seattle, WA, USA. Electronic address: matthias@liai.org.
authors.forename: Matthias
authors.initials: M
authors.lastname: von Herrath
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000473:pathology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
chemical_list: D001324:Autoantigens; D007371:Interferon-gamma
keywords: Antigen specific T-cells; CD8(+) T-cells; ELISpot; HLA-Qdot-multimer analysis; Type 1 diabetes