Faculty Collaboration Database

The Presence and Preferential Activation of Regulatory T Cells Diminish Adoptive Transfer of Autoimmune Diabetes by Polyclonal Nonobese Diabetic (NOD) T Cell Effectors into NSG versus NOD-scid Mice. J Immunol 2015 Oct 01;195(7):3011-9

Date

08/19/2015

Pubmed ID

26283479

Pubmed Central ID

PMC4575869

DOI

10.4049/jimmunol.1402446

Scopus ID

2-s2.0-84942436455 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

NOD-scid.Il2rg(null) (NSG) mice are currently being used as recipients to screen for pathogenic autoreactive T cells in type 1 diabetes (T1D) patients. We questioned whether the restriction of IL-2R γ-chain (Il-2rγ)-dependent cytokine signaling only to donor cells in NSG recipients differently influenced the activities of transferred diabetogenic T cells when they were introduced as a monoclonal/oligoclonal population versus being part of a polyclonal repertoire. Unexpectedly, a significantly decreased T1D transfer by splenocytes from prediabetic NOD donors was observed in Il-2rγ(null)-NSG versus Il-2rγ-intact standard NOD-scid recipients. In contrast, NOD-derived monoclonal/oligoclonal TCR transgenic β cell-autoreactive T cells in either the CD8 (AI4, NY8.3) or CD4 (BDC2.5) compartments transferred disease significantly more rapidly to NSG than to NOD-scid recipients. The reduced diabetes transfer efficiency by polyclonal T cells in NSG recipients was associated with enhanced activation of regulatory T cells (Tregs) mediated by NSG myeloid APC. This enhanced suppressor activity was associated with higher levels of Treg GITR expression in the presence of NSG than NOD-scid APC. These collective results indicate NSG recipients might be efficiently employed to test the activity of T1D patient-derived β cell-autoreactive T cell clones and lines, but, when screening for pathogenic effectors within polyclonal populations, Tregs should be removed from the transfer inoculum to avoid false-negative results.

Author List

Presa M, Chen YG, Grier AE, Leiter EH, Brehm MA, Greiner DL, Shultz LD, Serreze DV

Author

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adoptive Transfer
Animals
B-Lymphocytes
CD8-Positive T-Lymphocytes
Diabetes Mellitus, Type 1
Female
Glucocorticoid-Induced TNFR-Related Protein
Mice
Mice, Inbred NOD
Mice, SCID
Receptors, Interleukin-2
Signal Transduction
Spleen
T-Lymphocytes, Regulatory