Prevention of type 1 diabetes by gene therapy
J. Clin. Invest. Chaorui Tian, et al. 114:969 doi:10.1172/JCI22103 [
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Figure 7Expression of retrovirally transduced diabetes-resistant MHC class II genes in bone marrow_derived cells prevents the development of functional autoreactive T cells in NOD mice. Twenty to twenty-eight weeks after reconstitution, splenocytes were harvested from NOD mice reconstituted with MMP-IAβ-d-GFP_, MMP-IAβ-k-GFP_, or control MMP-GFP_transduced bone marrow. Single-cell suspensions were prepared and cultured overnight with whole insulin protein, GAD 65 peptide 206_220, or, as a control, peptide 85_99 of MBP. The frequency of cells producing IFN-γ (
A), IL-2 (
B), and IL-4 (
C) was then measured by cytokine ELISPOT assays. Responses to GAD 65 or insulin by splenocytes from NOD mice reconstituted with MMP-GFP_transduced bone marrow (black bars) were compared with responses to GAD 65 or insulin by cells from NOD mice reconstituted with either MMP-IAβ-d-GFP_ or MMP-IAβ-k-GFP_transduced bone marrow (white bars). Shown is 1 representative experiment of 3.