International Immunology, Vol. 12, No. 8, 1205-1215,
August 2000
© 2000 Japanese Society for Immunology
Molecular mechanism of the impairment in activation signal transduction in CD4+ T cells from old mice
Department of Allergology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
1 Department of Membrane Biochemistry, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan
2 Department of Pathology and Immunology, Tokyo Medical and Dental University School of Medicine, Tokyo 113-8510, Japan
3 Laboratory Animal Research Facilities, National Institute for Longevity Sciences, Aichi 474-8511, Japan
4 Department of Physiology, Tokyo Women's Medical College, Tokyo 162-8666, Japan
Correspondence to: T. Tamura
It is well known that IL-2 production of CD4+ T cells from old mice (old T cells) is impaired. In this study, we have examined TCR complex 
chain expression of old T cells and their TCR downstream signal transduction pathways stimulated with anti-CD3. Activation of protein tyrosine kinases, Fyn and ZAP-70, and turnover of inositol phosphates stimulated with anti-CD3 were severely impaired in old T cells, although levels of these proteins were comparable to those in young T cells. Increase in intracellular Ca2+ concentration in old T cells was also impaired. Old T cells starting the Ca2+ oscillation by the anti-CD3 stimulation were severely decreased in number and the oscillation waves were broader in shape. T cells with –Fc
R
heterodimer in the TCR–CD3 complex were increased in proportion in old T cells with a concomitant decrease in the T cells with - homodimer. The density of the TCR–CD3 complex on old T cells was confirmed to be comparable to that on young T cells. The impairment in TCR downstream signal transduction pathways and the increase in –FcR heterodimer in the TCR–CD3 complex were confirmed to be the situation in Th1 clones established from old mice. These results indicate that old T cells are impaired in response to TCR stimulation, because T cells with the TCR–CD3 complex containing the –FcR heterodimer are increased in proportion in old T cells.
Keywords: protein kinase, signal transduction, T lymphocytes, TCR
5 Present address: Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd, Osaka 554-8558, Japan
6 Present address: Department of Biology, Sunchon National University, Sunchon 540-742, Republic of Korea
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