We previously reported that continuous 24-month co-stimulation blockade by abatacept significantly slows decline of β-cell function after diagnosis of Type 1 diabetes. In a mechanistic extension of that study, we evaluated peripheral blood immune cell subsets (CD4, CD8 naïve, memory and activated subsets, myeloid and plasmacytoid dendritic cells, monocytes, B lymphocytes, CD4+CD25high regulatory T-cells and invariant NK T-cells) by flow cytometry at baseline, 3, 6, 12, 24 and 30 months after treatment initiation to discover biomarkers of therapeutic effect. Using multivariable analysis and lagging of longitudinally measured variables we made the novel observation in the placebo group that an increase in central memory (CM) CD4 T-cells (CD4+CD45R0+CD62L+) during a preceding visit was significantly associated with C-peptide decline at the subsequent visit. These changes were significantly affected by abatacept treatment, which drove peripheral contraction of CM CD4 T-cells and expansion of naïve (CD45R0-CD62L+) CD4 T-cells in association with a significantly slower rate of C-peptide decline. The findings show that the quantification of CM CD4 T-cells can provide a surrogate immune marker for C-peptide decline after diagnosis of Type 1 diabetes, and that co-stimulation blockade may exert its beneficial therapeutic effect via modulation of this subset.
- Received January 11, 2014.
- Accepted May 15, 2014.
- © 2014 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.