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Hyperglycemia does not affect antigen specific activation and cytolytic killing by CD8+ T cells in vivo

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Recino, A 
Barkan, K 
Wong, FS 

Abstract

Metabolism is of central importance to T cell survival and differentiation. It is well known that T cells cannot function in the absence of glucose, but it is less clear how they respond to excessive levels of glucose. In this study we investigated how increasing levels of glucose affect T cell-mediated immune responses. We examined the effects of increased levels of glucose on CD8⁺ T cell behaviour in vitro by assessing activation and cytokine production, as well as oxygen consumption rate, extracellular acidification rate and intracellular signalling. In addition, we assessed in vivo proliferation, cytokine production and cytolytic activity of cells in chemically induced diabetic C57BL6 mice. Elevated levels of glucose in in vitro cultures had modest effects on proliferation and cytokine production, while in vivo hyperglycemia had no effect on CD8⁺ T cell proliferation, interferon gamma production or cytolytic killing.

Description

Keywords

T-cells, diabetes, hyperglycaemia, immunometabolism, mouse models, Animals, Antigens, CD8-Positive T-Lymphocytes, Diabetes Mellitus, Experimental, Hyperglycemia, Interferon-gamma, Lymphocyte Activation, Mice, Oxygen Consumption

Journal Title

Bioscience Reports

Conference Name

Journal ISSN

0144-8463
1573-4935

Volume Title

37

Publisher

Portland Press, Biochemical Society
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M00015X/2)
Isaac Newton Trust (1238(r))
Diabetes UK (None)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/M001083/1)
British Council in Israel (02BX12ACYD)
Diabetes Research & Wellness Foundation (DRWF) (SCA/OF/12/13)
Leverhulme Trust (EM-2015-030)
This work was supported by the NC3Rs [grant number NC/M001083/1]; the BBSRC [grant number BB/M00015X/2]; the Leverhulme Trust [grant number EM-2015-030]; the Medical Research Council [grant number G0901155]; the Diabetes U.K. [grant number BDA 09/0003840]; the BBSRC-funded Midlands Integrative Biosciences Training Partnership (MIBTP) (K.B.); and the Lollipop Foundation (M.W. as the main grant applicant and A.R. as a co-applicant).