Coculture of Th cells with interleukin (IL)-7 in the absence of antigenic stimuli induced T-cell anergy reversed by IL-15.
Interleukin-7 (IL-7) is an important survival factor for T cells. We report here for the first time that it has another important role, facilitating T-cell clonal unresponsiveness, or anergy. The anergy was induced by a 20-day coculture of activated-human CD4(+) T-cell clones with IL-7 and irradiated peripheral blood mononuclear cells without antigenic stimuli. T-cell survival, but not T-cell anergy induction, was dependent on direct cell contacts between T cells and irradiated peripheral blood mononuclear cells. The anergic T cells exhibited no or very low expression of IL-7 receptor alpha chain (IL-7Ralpha), IL-2 receptor alpha chain (IL-2Ralpha), and common gamma chain (gammac), and did not express cytotoxic T-lymphocyte-associated protein 4, but expressed IL-15Ralpha. Coculture for 3 to 9 days of anergic T cells with a T-cell-activating cytokine IL-15, but not IL-2, restored the responsiveness of IL-7-induced anergic T cells together with reexpressions of IL-7Ralpha, IL-2Ralpha, and gammac. The anergy induction by IL-7 and restoration of responsiveness by IL-15 suggest novel mechanisms for regulation of helper T-cell responses, induction of peripheral tolerance, and breakdown of T-cell self-tolerance.
Chen
Yu-Zhen
YZ
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. chenyuz@kaiju.medic.kumamoto-u.ac.jp
Lai
Zhong-Fang
ZF
Nishimura
Yasuharu
Y
D000941:Antigens / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D017635:Clonal Anergy / Q000502:physiology*; D018920:Coculture Techniques; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D019409:Interleukin-15; D015851:Interleukin-7; D011994:Recombinant Proteins