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Blood, 15 January 2002, Vol. 99, No. 2, pp. 555-560
IMMUNOBIOLOGY
CD4+CD25+ T-cell development is regulated
by at least 2 distinct mechanisms
Akira Suto,
Hiroshi Nakajima,
Kei Ikeda,
Shuichi Kubo,
Toshinori Nakayama,
Masaru Taniguchi,
Yasushi Saito, and
Itsuo Iwamoto
From the Department of Internal Medicine II, the Core
Research for Evolutional Science and Technology Project, and the
Department of Molecular Immunology, Graduate School of Medicine, Chiba
University, Japan; and the Department of Immunology, Tokyo Metropolitan
Institute of Medical Science, Tokyo Metropolitan Organization for
Medical Research, Japan.
It has recently been shown that
CD4+CD25+ T cells are immunoregulatory T cells
that prevent CD4+ T-cell-mediated organ-specific
autoimmune diseases. In this study, the regulatory mechanism of
CD4+CD25+ T-cell development were investigated
using T-cell receptor (TCR) transgenic mice. It was found that
CD4+CD25+ T cells preferentially expressed the
endogenous TCR chain in DO10+ TCR transgenic mice
compared with CD4+CD25 T cells. Moreover, it
was found that CD4+CD25+ thymocytes were
severely decreased in DO10+ TCR-/ mice
in positively selecting and negatively selecting backgrounds, whereas
CD4+CD25 thymocytes efficiently developed by
transgenic TCR in DO10+ TCR-/ mice in
positively selecting backgrounds, indicating that the appropriate
affinity of TCR to major histocompatibility complex (MHC) for the
development of CD4+CD25+ thymocytes is
different from that of CD4+CD25 thymocytes
and that a certain TCR-MHC affinity is required for the development of
CD4+CD25+ thymocytes. Finally, it was found
that, in contrast to thymus, CD4+CD25+ T cells
were readily detected in spleen of DO10+
TCR-/ mice in positively selecting backgrounds and
that splenic CD4+CD25+ T cells, but not
CD4+CD25+ thymocytes, were significantly
decreased in B-cell-deficient mice, suggesting that B cells may
control the peripheral pool of CD4+CD25+ T
cells. Together, these results indicate that the development of
CD4+CD25+ T cells in thymus and the homeostasis
of CD4+CD25+ T cells in periphery are regulated
by distinct mechanisms.
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