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J Autoimmun. 2014 May;50:77-82. doi: 10.1016/j.jaut.2013.12.003. Epub 2013 Dec 30.

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.

Author information

1
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
2
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; University of California San Diego, San Diego, CA, USA.
3
University of California San Diego, San Diego, CA, USA.
4
Novo Nordisk Type 1 Diabetes R & D Center, Seattle, WA, USA.
5
Ayasdi, Inc., Palo Alto, CA, USA.
6
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.

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.

KEYWORDS:

Antigen specific T-cells; CD8(+) T-cells; ELISpot; HLA-Qdot-multimer analysis; Type 1 diabetes

PMID:
24387802
DOI:
10.1016/j.jaut.2013.12.003
[Indexed for MEDLINE]

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