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International Immunology, Vol. 14, No. 8, pp. 857-865, August 2002
© 2002 Japanese Society for Immunology

Development of CD25+ T cells secreting transforming growth factor-ß1 by altered peptide ligands expressed as self-antigens

Hiromichi Yamashiro1, Nobumichi Hozumi1 and Naoko Nakano1

1 Research Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda City, Chiba 278-0022, Japan

Correspondence to: N. Nakano; E-mail: naoko{at}rs.noda.sut.ac.jp
Transmitting editor: K. Inaba

This study demonstrates that CD4+ T cells specific for an altered self-antigen differentiate to T cells secreting transforming growth factor (TGF)-ß1. In this study, we utilized mice expressing an altered peptide ligand containing a single amino acid substitution of moth cytochrome c 88–103 peptide. In these mice, antigen-specific T cells escaping thymic negative selection differentiated into T cells with an effector/memory phenotype, CD44high, CD45RBlow, CD62L– and CD25intermediate. The expression of CD25 and high levels of CD44 was initiated in the thymus during the development from CD4+CD8+ to CD4+; a large proportion of maturing CD4+ thymocytes expressed both CD25 and high levels of CD44. Upon antigen stimulation, CD4+ T cells derived from these mice did not proliferate or secrete IL-2, but secreted TGF-ß1. Neutralizing antibodies to TGF-ß1 reversed the impaired proliferative responses to the antigen, suggesting that TGF-ß1 secreted from these T cells negatively regulates T cell responses.

Keywords: altered peptide ligands, self-antigen, transforming growth factor-ß1


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