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Affinity for self antigen selects Treg cells with distinct functional properties
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4393081
Author(s)
Wyss, L.; Stadinski, B. D.; King, C. G.; Schallenberg, S.; McCarthy, N. I.; Lee, J. Y.; Kretschmer, K.; Terracciano, L. M.; Anderson, G.; Surh, C. D.; Huseby, E. S.; Palmer, E.
The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells zsuper< T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping regulatory activities.
