Schnurri-2 controls memory Th1 and Th2 cell numbers in vivo.
Schnurri-2 (Shn-2) is a large zinc-finger containing protein, and it plays a critical role in cell growth, signal transduction and lymphocyte development. In Shn-2-deficient CD4 T cells, the activation of NF-kappaB was up-regulated and their ability to differentiate into Th2 cells was enhanced. We herein demonstrate that Th1 and Th2 memory cells are not properly generated from Shn-2-deficient effector Th1/Th2 cells. Even a week after the transfer of effector Th1/Th2 cells into syngeneic mice, a dramatic decrease in the number of Shn-2-deficient donor T cells was detected particularly in the lymphoid organs. The transferred Shn-2-deficient Th1/Th2 cells express higher levels of the activation marker CD69. No significant defect in the BrdU incorporation in the Shn-2-deficient transferred CD4 T cells was observed. The numbers of apoptotic cells were selectively higher in Shn-2-deficient donor Th1/Th2 cell population. Moreover, Shn-2-deficient effector Th1 and Th2 cells showed an increased susceptibility to cell death in in vitro cultures with increased expression of FasL. Transfer of Th2 effector cells over-expressing the p65 subunit of NF-kappaB resulted in a decreased number of p65-expressing cells in the lymphoid organs. As expected, T cell-dependent Ab responses after in vivo immunization of Shn-2-deficient mice were significantly reduced. Thus, Shn-2 appears to control the generation of memory Th1/Th2 cells through a change in their susceptibility to cell death.
Kimura
Motoko Y
MY
Department of Immunology, Graduate School of Medicine, Chiba University, Japan.
Iwamura
Chiaki
C
Suzuki
Akane
A
Miki
Takako
T
Hasegawa
Akihiro
A
Sugaya
Kaoru
K
Yamashita
Masakatsu
M
Ishii
Shunsuke
S
Nakayama
Toshinori
T
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000502:physiology*; D007156:Immunologic Memory; D037181:Lectins, C-Type; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D051996:Transcription Factor RelA / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D051996:Transcription Factor RelA; D019014:fas Receptor; D000099192:CD69 Antigens; C490430:Hivep2 protein, mouse