Molecular mechanisms for Kv1.3 potassium channel current inhibition by CD3/CD28 stimulation in Jurkat T cells.
In T lymphocyte, activation of Kv1.3 channel, the major voltage-dependent K(+) channel, is an essential step for cell proliferation in immune responses. Here, effects of anti-CD3 and anti-CD28 antibodies on Kv1.3 current were examined in three types of human T lymphocyte derived cell lines, Jurkat E6-1, p56lck-kinase deficient mutant JCaM.1, and CD45-phosphatase deficient mutant J45.01. Kv1.3 current was partly reduced by CD3 stimulation and more strongly by addition of anti-CD28 antibody in E6-1. In JCaM.1, Kv1.3 current responses to anti-CD28/CD3 antibodies were similar to those in E6-1. In J45.01, CD3 stimulation partly inhibited Kv1.3 current, but the additive reduction by CD28 stimulation was not significant. The inhibition of tyrosine phosphatase in E6-1 abolished the additional inhibition by anti-CD28 antibody in a similar manner as in J45.01. In conclusion, the stimulation of CD28 in addition to CD3 strongly inhibits Kv1.3 current and this additive inhibition is mediated by CD45 activation.
Matsushita
Yuichiro
Y
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya 467-8603, Japan.
Ohya
Susumu
S
Itoda
Haruna
H
Kimura
Takuya
T
Suzuki
Yoshiaki
Y
Yamamura
Hisao
H
Imaizumi
Yuji
Y
D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000187:drug effects / Q000276:immunology*; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D017493:Leukocyte Common Antigens / Q000276:immunology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D051664:Kv1.3 Potassium Channel; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D017027:Protein Tyrosine Phosphatases