CD25- T Cells Generate CD25+Foxp3+ Regulatory T Cells by Peripheral Expansion

• Published in: The Journal of immunology (1950) 2004-12, Vol.173 (12), p.7259-7268
• Main Authors: Curotto de Lafaille, Maria A, Lino, Andreia C, Kutchukhidze, Nino, Lafaille, Juan J
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Animals, Newborn; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; Cell Proliferation; Cells, Cultured; Clonal Anergy; DNA-Binding Proteins - biosynthesis; Forkhead Transcription Factors; Interleukin-2 - biosynthesis; Interleukin-2 - physiology; Kinetics; Lymphoid Tissue - immunology; Lymphoid Tissue - metabolism; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Receptors, Interleukin-2 - biosynthesis; Receptors, Interleukin-2 - metabolism; Resting Phase, Cell Cycle - immunology; Signal Transduction - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - transplantation; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.12.7259

Naturally occurring CD4(+) regulatory T cells are generally identified through their expression of CD25. However, in several experimental systems considerable T(reg) activity has been observed in the CD4(+)CD25(-) fraction. Upon adoptive transfer, the expression of CD25 in donor-derived cells is not stable, with CD4(+)CD25(+) cells appearing in CD4(+)CD25(-) T cell-injected animals and vice versa. We show in this study that CD25(+) cells arising from donor CD25(-) cells upon homeostatic proliferation in recipient mice express markers of freshly isolated T(reg) cells, display an anergic state, and suppress the proliferation of other cells in vitro. The maintenance of CD25 expression by CD4(+)CD25(+) cells depends on IL-2 secreted by cotransferred CD4(+)CD25(-) or by Ag-stimulated T cells in peripheral lymphoid organs.