Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice.
The class IV semaphorin Sema4A provides a costimulatory signal to T cells. To investigate the possible developmental and regulatory roles of Sema4A in vivo, we generated Sema4A-deficient mice. Although Sema4A-deficient mice develop normally, DCs and T cells from knockout mice display poor allostimulatory activities and T helper cell (Th) differentiation, respectively. Interestingly, in addition to its expression on DCs, Sema4A is upregulated on Th1-differentiating cells, and it is necessary for in vitro Th1 differentiation and T-bet expression. Consequently, in vivo antigen-specific T cell priming and antibody responses against T cell-dependent antigens are impaired in the mutant mice. Additionally, Sema4A-deficient mice exhibit defective Th1 responses. Furthermore, reconstitution studies with antigen-pulsed DCs reveal that DC-derived Sema4A is important for T cell priming, while T cell-derived Sema4A is involved in developing Th1 responses. Collectively, these results indicate a nonredundant role of Sema4A not only in T cell priming, but also in the regulation of Th1/Th2 responses.
Kumanogoh
Atsushi
A
Department of Molecular Immunology and CREST Program of JST, Research Institute for Microbial DiseasesOsaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Shikina
Takashi
T
Suzuki
Kazuhiro
K
Uematsu
Satoshi
S
Yukawa
Kazunori
K
Kashiwamura
Shin-Ichiro
S
Tsutsui
Hiroko
H
Yamamoto
Midori
M
Takamatsu
Hyota
H
Ko-Mitamura
Elizabeth P
EP
Takegahara
Noriko
N
Marukawa
Satoko
S
Ishida
Isao
I
Morishita
Hiroshi
H
Prasad
Durbaka V R
DV
Tamura
Manabu
M
Mizui
Masayuki
M
Toyofuku
Toshihiko
T
Akira
Shizuo
S
Takeda
Kiyoshi
K
Okabe
Masaru
M
Kikutani
Hitoshi
H
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D018390:Gene Targeting; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D039961:Semaphorins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D039961:Semaphorins