TY - JOUR
T1 - Abnormal T cell frequencies, including cytomegalovirus - Associated expansions, distinguish seroconverted subjects at risk for type 1 diabetes
AU - Harms, Robert Z.
AU - Lorenzo-Arteaga, Kristina M.
AU - Ostlund, Katie R.
AU - Smith, Victoria B.
AU - Smith, Lynette M.
AU - Gottlieb, Peter
AU - Sarvetnick, Nora
N1 - Funding Information:
Samples were obtained from the TrialNet Biorepository through an ancillary study to the TrialNet Pathway to Prevention Study (TN-01) currently funded by NIH grants U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085461, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, and the Juvenile Diabetes Research Foundation International (JDRF). The UNMC Flow Cytometry Research Facility is administrated through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffett Cancer Center’s National Cancer Institute Cancer Support Grant. Major instrumentation has been provided by the Office of the Vice Chancellor for Research, The University of Nebraska Foundation, the Nebraska Banker’s Fund, and by the NIH-NCRR Shared Instrument Program.
Funding Information:
This work was supported by grants to NS from NIAD (UO1AI130841, UO1AI102012), the Leona M. and Harry B.
PY - 2018/10/22
Y1 - 2018/10/22
N2 - We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjects also possessed decreased frequencies of CCR4-expressing CD4 T cells, including a regulatory-like subset. Interestingly, we found an elevation of CD57+, CD28-, CD127-, CD27- CD8 T cells (SLEC) among seroconverted subjects that was most pronounced among those that progressed to disease. The frequency of these SLEC was strongly correlated with CMV IgG abundance among seroconverted subjects, associated with IA-2 levels, and most elevated among CMV+ seroconverted subjects who progressed to disease. Combined, our data indicate discrete, yet profound T cell alterations are associated with islet autoimmunity among at-risk subjects.
AB - We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjects also possessed decreased frequencies of CCR4-expressing CD4 T cells, including a regulatory-like subset. Interestingly, we found an elevation of CD57+, CD28-, CD127-, CD27- CD8 T cells (SLEC) among seroconverted subjects that was most pronounced among those that progressed to disease. The frequency of these SLEC was strongly correlated with CMV IgG abundance among seroconverted subjects, associated with IA-2 levels, and most elevated among CMV+ seroconverted subjects who progressed to disease. Combined, our data indicate discrete, yet profound T cell alterations are associated with islet autoimmunity among at-risk subjects.
KW - Autoimmunity
KW - CD4 T cells
KW - CD8 T cells
KW - Cytomegalovirus-HCMV
KW - Mucosal associated invariant T cells (MAIT)
KW - T regulatory cells (Treg)
KW - TrialNet
KW - Type 1 diabetes (T1D)
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U2 - 10.3389/fimmu.2018.02332
DO - 10.3389/fimmu.2018.02332
M3 - Article
C2 - 30405601
AN - SCOPUS:85055786409
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - OCT
M1 - 2332
ER -