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Induction of self‐antigen‐specific Foxp3 + regulatory T cells in the periphery by lymphodepletion treatment with anti‐mouse thymocyte globulin in mice
Author(s) -
Lu Yan,
Suzuki Jun,
Guillioli Maria,
Umland Oliver,
Chen Zhibin
Publication year - 2011
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/j.1365-2567.2011.03466.x
Subject(s) - immunology , thymocyte , foxp3 , biology , antigen , globulin , cd8 , immune system
Summary Lymphodepletion therapies are increasingly tested for controlling immune damage. One appealing premise for such a therapy is that it may ‘reboot’ the immune system and restore immune tolerance. However, the tolerogenic potential of lymphodepletion therapies remains controversial. The debate is exemplified by conflicting evidence from the studies of anti‐thymocyte globulin (ATG), a prototype of immunodepleting drugs, in particular on whether it induces CD4 + CD25 + Foxp3 + regulatory T (Treg) cells. To understand the impact of ATG on T cells at a clonal level in vivo , we studied the effect of anti‐mouse thymocyte globulin (mATG) in a reductionist model in which the T‐lymphocyte repertoire consists of a single clone of pathogenic T effector (Teff) cells specific to a physiological self‐antigen. The mATG treatment led to peripheral induction of antigen‐specific Treg cells from an otherwise monoclonal Teff repertoire, independent of thymic involvement. The de novo induction of Treg cells occurred consistently in local draining lymph nodes, and persistence of induced Treg cells in blood correlated with long‐term protection from autoimmune destruction. This study provides in vivo evidence for clonal conversion from a pathogenic self‐antigen‐specific Teff cell to a Treg cell in the setting of immunodepletion therapies.