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Enhanced renewal of regulatory T cells in relation to CD 4 + conventional T lymphocytes in the peripheral compartment
Author(s) -
Nogueira Jeane de Souza,
Canto Fábio Barrozo do,
Nunes Caroline Fraga Cabral Gomes,
Vianna Pedro Henrique Oliveira,
Paiva Luciana de Souza,
Nóbrega Alberto,
Bellio Maria,
Fucs Rita
Publication year - 2016
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12555
Subject(s) - foxp3 , biology , homeostasis , microbiology and biotechnology , immunology , thymic involution , cell , population , t cell , immune system , medicine , genetics , environmental health
Summary CD 4 + Foxp3 + regulatory T (Treg) cells are necessary for the maintenance of self‐tolerance and T‐cell homeostasis. This population is kept at stable frequencies in secondary lymphoid organs for the majority of the lifetime, despite permanent thymic emigration or in the face of thymic involution. Continuous competition is expected to occur between recently thymus‐emigrated and resident Treg cells (either natural or post‐thymically induced). In the present work, we analysed the renewal dynamics of Treg cells compared with CD4 + Foxp3‐ conventional T cells (Tconv), using protocols of single or successive T‐cell transfers into syngeneic euthymic or lymphopenic ( nu/nu or RAG 2 −/− ) mice, respectively. Our results show a higher turnover for Treg cells in the peripheral compartment, compared with Tconv cells, when B cell‐sufficient euthymic or nude hosts are studied. This increased renewal within the Treg pool, shown by the greater replacement of resident Treg cells by donor counterparts, correlates with augmented rates of proliferation and is not modified following temporary environmental perturbations induced by inflammatory state or microbiota alterations. Notably, the preferential substitution of Treg lymphocytes was not observed in RAG 2 −/− hosts. We showed that limited B‐cell replenishment in the RAG 2 −/− hosts decisively contributed to the altered peripheral T‐cell homeostasis. Accordingly, weekly transfers of B cells to RAG 2 −/− hosts rescued the preferential substitution of Treg lymphocytes. Our study discloses a new aspect of T‐cell homeostasis that depends on the presence of B lymphocytes to regulate the relative incorporation of recently arrived Treg and Tconv cells in the peripheral compartment.