Inducing and expanding regulatory T cell populations by foreign antigen

Nature Immunology 6, 1219 - 1227 (2005)

Speaker : 林嬿琳                                             Time : 13:00-14:00,Mar. 01, 2006

Commentator : 黎煥耀老師                                Place : Room 601

Abstract:

It is well known that CD4⁺CD25⁺FOXP3⁺ regulatory T cells maintain peripheral tolerance and prevents autoimmune diseases, but whether the peripheral generation of CD4⁺CD25⁺FOXP3⁺regulatory T cells was achieved is uncertain. Continuing previous studies, the author adoptively transferred sorted naive CD4⁺CD25^- T cells from Rag2^-/- 6.5 TCR-transgenic Thy-1.2⁺ mice into normal Thy-1.1⁺ BALB/c recipients and on the next day intraperitoneally injected recipient mice with a single dose (40 ng) of anti-DEC/HA (109-117). Analysis of recipients 14 day after injection of antibodies, they found this process could induce these naïve T cells to become antigen-specific CD4⁺CD25⁺FOXP3⁺ T cells. Not only they could express the lineage marker FOXP3 but also had the antigen-specific suppressive function in vivo. Moreover, 40 ng of anti-DEC/HA (109-117) was the most efficient dose to mediate this conversion, independent of CD40 signaling. In the same experiment protocol, impaired TGF-bR signaling diminished conversion of naïve CD4⁺CD25^- T cells into CD4⁺CD25⁺FOXP3⁺ regulatory T cells. On the contrary, the conversion rate of naïveCD4⁺CD25^- T cells from IL-2^-/- 6.5 TCR-transgenic Thy-1.2⁺ mice into CD4⁺CD25⁺FOXP3⁺ regulatory T cells was more efficient than from wild-type Rag2^-/-6.5 TCR-transgenic mice. This hinted the quantity of IL-2 may affect the conversion of naïve CD4⁺CD25^- T cells into CD4⁺CD25⁺FOXP3⁺ regulatory T cells. In summary, the author showed a possible link between proliferation and conversion in a variety of different conditions.

References:

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2. Apostolou, I. & von Boehmer, H. In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med. 199, 1401–1408 (2004). 
3. Kretschmer, K., Apostolou, I., Hawiger, D., Khazaie, K., Nussenzweig MC, & von Boehmer, H. Inducing and expanding regulatory T cell populations by foreign antigen. Nature Immunology 6, 1219 - 1227 (2005)