Costimulation of T-cell proliferation by anti-L-selectin antibody is associated with the reduction of a cdk inhibitor p27.
In this study, we investigated the costimulatory activity of l-selectin in primary mouse T cells. Proliferation induced by immobilized anti-CD3 antibody was enhanced by immobilized anti-l-selectin antibody. In contrast to the anti-CD28 antibody, anti-l-selectin antibody did not enhance interleukin-2 (IL-2) expression. One of the cyclin-dependent kinase (cdk) inhibitors, p27, was reduced by costimulation with anti-l-selectin antibody, as with anti-CD28 antibody, suggesting that the enhancement of T-cell proliferation is the result of a reduced p27 level. Since anti-l-selectin antibody enhanced the activation of extracellular signal-regulated protein kinase (ERK) induced by anti-CD3 antibody, ERK plays an important role in signal integration during costimulation. These results suggest that the mechanism of T-cell costimulation is at least partially different between CD28 and l-selectin, although the two mechanisms share a common downstream event, a reduction of p27 level, as a critical biochemical event in the cell cycle progression of T cells.
Nishijima
Ken-Ichi
K
Department of Biotechnology, Nagoya University, Nagoya, Japan. nishijma@proc.nubio.nagoya-u.ac.jp
Ando
Munetoshi
M
Sano
Shusuke
S
Hayashi-Ozawa
Aiko
A
Kinoshita
Yoshinori
Y
Iijima
Shinji
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D018089:Superantigens; D019041:L-Selectin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases