Generation of anergic and regulatory T cells following prolonged exposure to a harmless antigen.

Journal article

Regulatory CD4(+) T cells are known to develop during the induction of donor-specific peripheral tolerance to transplanted tissues; it is proposed that such tolerance is a consequence of persistent, danger-free stimulation by Ag. To test this hypothesis, male RAG-1(-/-) mice were recolonized with small numbers of monospecific CD4(+) T cells specific for the male H-2E(k)-restricted Ag Dby. After 6 wk in the male environment, the monospecific CD4(+) T cells, having recolonized the host, had become anergic to stimulation in vitro and had acquired a regulatory capacity. CD4(+) T cells in these mice expressed higher levels of CTLA-4 and glucocorticoid-induced TNF-related receptor than naive CD4(+) T cells, but only 3% of the recolonizing cells were CD25(+) and did not express significant foxP3 mRNA. In vivo, these tolerant T cells could censor accumulation of, and IFN-gamma production by, naive T cells, with only a slight inhibition of proliferation. This suppressive effect was not reversed by the addition of fresh bone marrow-derived male dendritic cells. These results suggest that persistent exposure to Ag in conditions that fail to evoke proinflammatory stimuli leads to the development of T cells that are both anergic and regulatory.

Authors: Chen, T; Cobbold, S; Fairchild, P; Waldmann, H

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 172
• Issue: 10
• Pages: 5900-5907
• Publication date: 2004-05-01
• DOI: 10.4049/jimmunol.172.10.5900
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Graft vs Host Disease; Molecular Sequence Data; Cell Division; Clonal Anergy; Mice; Proteins; Female; Male; Mice, Inbred CBA; DEAD-box RNA Helicases; Coculture Techniques; Amino Acid Sequence; Immunophenotyping; Interphase; Antigens; Homeodomain Proteins; Mice, Transgenic; CD4-Positive T-Lymphocytes; Cell Differentiation; Mice, Knockout; RNA, Messenger; Spleen; Animals; Mice, Inbred C57BL; T-Lymphocyte Subsets; Adoptive Transfer