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Activating and inhibitory Fcγ receptors can differentially modulate T cell‐mediated autoimmunity
Author(s) -
Iruretagoyena Mirentxu I.,
Riedel Claudia A.,
Leiva Eduardo D.,
Gutiérrez Miguel A.,
Jacobelli Sergio H.,
Kalergis Alexis M.
Publication year - 2008
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200838197
Subject(s) - experimental autoimmune encephalomyelitis , adoptive cell transfer , myelin , immunology , biology , autoimmunity , t cell , receptor , myelin basic protein , antigen , multiple sclerosis , microbiology and biotechnology , t cell receptor , immune system , neuroscience , central nervous system , biochemistry
Abstract The molecular bases responsible for the loss of T cell tolerance to myelin antigens leading to the onset of multiple sclerosis remain obscure. It has been shown that balanced signaling through activating and inhibitory receptors is critical for the maintenance of tolerance to self antigens in autoimmune disorders. However, although FcγR have been shown to influence experimental autoimmune encephalomyelitis (EAE) development, their role during pathogenesis remains controversial. Here we have evaluated whether relative expression of activating (FcγRIII) and inhibitory (FcγRIIb) FcγR can modulate myelin‐specific T cell response, as well as the susceptibility to develop EAE in mice. While FcγRIIb –/– mice showed a significant increase in EAE severity, an FcγRIII deficiency protected mice from disease. In addition, FcγRIIb –/– mice showed enhanced activation of myelin‐specific effector T cells, which were significantly more effective at causing EAE in adoptive transfer experiments than were T cells from wild‐type mice. In contrast, FcγRIII –/– mice showed a significantly reduced activation of myelin‐specific T cells and these cells failed to adoptively transfer EAE. Consistently, increased expansion of regulatory T cells (Treg) during EAE was observed only for FcγRIII –/– mice, which were able to suppress disease when adoptively transferred to recipient mice. These findings suggest that the balance between activating and inhibitory FcγR signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression.