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Updated: Jun 14, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Naive CD4+ T lymphocytes circulate through lymphoid organs to interact with endogenous antigens and upregulate their
Michio Tomura1, Kikuji Itoh, Osami Kanagawa
1Laboratory for Autoimmune Regulation, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama City, Japan.
Naive T lymphocytes recirculate through the lymph-vascular system and enter and exit lymphoid organs. Using mice expressing the photoconvertible fluorescence protein Kaede, we demonstrated that naive T cells seek to interact with endogenous Ags after migrating to the lymphoid organs. The interaction with endogenous Ags transiently induces CD69 expression on T cells, which prolongs retention in the lymphoid organs. Cells that fail to express CD69 or lose CD69 expression migrate to other lymphoid organs. Functionally, CD69(+)-naive CD4(+) T cells exhibit faster and greater cytokine production than do CD69(-) naive CD4(+) T cells. These results indicate that CD4(+) T cells continuously migrate to interact with endogenous Ags, and such an interaction plays an important role in the Ag reactivity of naive CD4(+) T cells.
Naive T lymphocytes recirculate through the lymph-vascular system and enter and exit lymphoid organs. Using mice expressing the photoconvertible fluorescence protein Kaede, we demonstrated that naive T cells seek to interact with endogenous Ags after migrating to the lymphoid organs. The interaction with endogenous Ags transiently induces CD69 expression on T cells, which prolongs retention in the lymphoid organs. Cells that fail to express CD69 or lose CD69 expression migrate to other lymphoid organs. Functionally, CD69(+)-naive CD4(+) T cells exhibit faster and greater cytokine production than do CD69(-) naive CD4(+) T cells. These results indicate that CD4(+) T cells continuously migrate to interact with endogenous Ags, and such an interaction plays an important role in the Ag reactivity of naive CD4(+) T cells.
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