Accuri C6 Flow Cytometer System
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0906565

Received for publication September 13, 2006.
Revised April 18, 2007.
Accepted for publication May 2, 2007.

Article

Hodgkin’s Reed-Sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells

Tsutomu Tanijiri , Toshiki Shimizu @, Kazutaka Uehira , Takashi Yokoi , Hideki Amuro , Hiroyuki Sugimoto , Yoshitaro Torii , Kenichirou Tajima , Tomoki Ito , Ryuichi Amakawa , and Shirou Fukuhara

The First Department of Internal Medicine, Kansai Medical University, Osaka, Japan

@ To whom correspondence should be addressed. E-mail: shimizto{at}takii.kmu.ac.jp.


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Abstract

A recent report revealed that a large population of Hodgkin’s lymphoma-infiltrating lymphocytes (HLILs) consisted of regulatory T cells. In this study, we cocultured CD4+ naive T cells with KM-H2, which was established as a Hodgkin’s Reed-Sternberg cell line, to clarify their ability to induce CD25+Forkhead box p3+ (Foxp3+) T cells. The characteristic analyses of T cells cocultured with KM-H2 revealed the presence of CD4+CD25+ T cells. They expressed CTLA-4, glucocorticoid-induced TNFR family-related gene, and Foxp3 and could produce large amounts of IL-10. Conversely, KM-H2 also generated CD4+ CTLs, which expressed Granzyme B and T cell intracellular antigen-1 in addition to Foxp3+ T cells. They exhibit a strong cytotoxic effect against the parental KM-H2. In conclusion, KM-H2 promotes a bidirectional differentiation of CD4+ naive T cells toward Foxp3+ T cells and CD4+ CTLs. In addition to KM-H2, several cell lines that exhibit the APC function were able to generate Foxp3+ T cells and CD4+ CTLs. Conversely, the APC nonfunctioning cell lines examined did not induce both types of cells. Our findings suggest that the APC function of tumor cells is essential for the differentiation of CD4+ naive T cells into CD25+Foxp3+ T cells and CD4+ CTLs and at least partly explains the predominance of CD25+Foxp3+ T cells in HLILs and their contribution to a better prognosis. Therefore, in APC-functioning tumors, including classical Hodgkin lymphomas, which generate Foxp3+ T cells and CD4+ CTLs, these T cell repertories play a beneficial role synergistically in disease stability.

Key Words: antigen-presenting cell • tumor surveillance • regulatory T cell • neoplastic cell