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The Potency of Allospecific Tregs Cells Appears to Correlate With T Cell Receptor Functional Avidity
Author(s) -
Tsang J. Y. S.,
Ratnasothy K.,
Li D.,
Chen Y.,
Bucy R. P.,
Lau K. F.,
Smyth L.,
Lombardi G.,
Lechler R.,
Tam P. K. H.
Publication year - 2011
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2011.03650.x
Subject(s) - avidity , t cell receptor , immunology , cd8 , adoptive cell transfer , il 2 receptor , transplantation , immunotherapy , t cell , regulatory t cell , cell therapy , antigen , cytotoxic t cell , medicine , biology , in vitro , immune system , cancer research , microbiology and biotechnology , stem cell , genetics
CD4 + CD25 + regulatory T cells (T reg cells) are an attractive adoptive cell therapy in mediating transplantation tolerance. T‐cell receptor (TcR) activation is critical for T reg function, suggesting that the TcR avidity of T reg cells used in therapy may affect the therapeutic outcome. To address this, we compared the regulatory capacity of T reg lines expressing TcRs derived from two TcR transgenic mice shown to have the same specificity but different functional avidities. T reg lines generated from CD4 + CD25 + T cells from C57BL/6 mice were transduced with one of either of these TcRs. The antigen specificity of the transduced T reg lines was confirmed in vitro . T reg lines expressing the TcR with higher functional avidity showed stronger suppressive capacity in a linked suppression model in vitro . Furthermore, the same T reg lines demonstrated a stronger proliferation in vivo following antigen exposure. Pretreatment of recipient BL/6 mice with these T reg cells, together with anti‐CD8 antibody and Rapamycin therapies, prolonged survival of BALB/c skins, as compared with mice that received T reg lines with lower TcR avidity. Taken together, these data suggest that the TcR functional avidity may be important for T reg function. It highlights the fact that strategies to select T reg with higher functional avidity might be beneficial for immunotherapy in transplantation.