Lymphopenia-driven CD8(+) T cells are resistant to antigen-induced tolerance in NOD.scid mice.
T cells undergoing lymphopenia-driven proliferation acquire effector and memory properties that can be pathogenic. Indeed, generalized lymphopenia is associated with a variety of autoimmune diseases such as type 1 diabetes. The current study was carried out to determine how CD8(+) T cells undergoing acute lymphopenic expansion respond to antigen under tolerizing conditions in vivo. Adoptive transfer of diabetes by TCR-transgenic CD8(+) T cells was enhanced following treatment of NOD. scid recipients with a high dose of soluble peptide. Furthermore, whereas TCR-transgenic CD8(+) T cells underwent clonal deletion and failed to differentiate into CTL in peptide-treated lymphoreplete recipient mice, TCR-transgenic CD8(+) T cells in a lymphopenic environment were resistant to clonal deletion, and CTL differentiation was enhanced by a high dose of soluble peptide. Moreover, peptide treatment had distinct effects on expression of the anti-apoptotic protein Bcl-X(L) in TCR-transgenic CD8(+) T cells under lymphopenic versus lymphoreplete conditions. These results demonstrate that CD8(+) T cells undergoing lymphopenia-driven expansion in NOD. scid recipients are resistant to antigen-induced tolerance, and readily differentiate into CTL upon stimulation with a high dose of soluble peptide.
Long
Brian
B
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Wong
Carmen P
CP
Wang
Yaming
Y
Tisch
Roland
R
D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D003920:Diabetes Mellitus / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000494:pharmacology; D007108:Immune Tolerance / Q000276:immunology*; D008231:Lymphopenia / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010446:Peptide Fragments / Q000494:pharmacology; D012995:Solubility
D000941:Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010446:Peptide Fragments