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MR Vol.11 No3 indexに戻る
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MODERN RHEUMATOLOGY
Vol.11 No.3 |
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Manipulation of costimulatory pathways in autoimmune
diseases |
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| A. Nakajima1 |
| (1) Department of Joint Disease and Rheumatism,
Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603,
Japan |
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| Abstract |
| Abstract There has recently been an increased
understanding of the role of costimulatory pathways in the activation
of the immune system and the maintenance of self-tolerance. It
has been suggested that the absence of costimulatory molecules
on normal tissue cells could serve to induce self-tolerance, and
that inappropriate expression of costimulatory molecules on antigen-presenting
cells (APCs) could activate self-reactive T cells, resulting in
autoimmunity. Among several costimulatory molecules characterized,
the interaction of CD28/CTLA4 on T cells with B7 (CD80 and CD86)
on APC appears to be of primary importance. In fact, inhibition
of the CD28-B7 interaction ameliorates several autoimmune diseases
in experimental animal models. However, differential roles for
CD80 and CD86 have been reported in certain conditions, and CTLA4
has been shown to play a negative role in T cell activation, suggesting
that the actual regulatory mechanisms of this pathway in autoimmunity
is much more complex. While the CD28-B7 interaction constitutes
a predominant pathway of T cell costimulation, some intact T cell
responses in CD28-deficient mice have suggested the presence of
alternative pathways. T cell-dependent immunity is also critically
regulated not only by other immunoglobulin superfamilies such as
B7RP-1/ICOS, but also by tumor necrosis factor (TNF) and TNF-receptor
superfamilies, which control immune responses in both a positive
and a negative fashion. Therefore, further investigation of the
physiological function of these costimulatory pathways in vivo
may help in developing rational therapeutic approaches for autoimmune
diseases. |
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| Key words |
Key words B7 related protein-1/inducible constimulator
(B7RP-1/ICOS) ・ CD28-B7 ・ Costimulation Programmed death-Ligand/programmed
death-1
(PD-L/PD-1) ・ Tumor necrosis factor and tumor necrosis factor receptor
(TNF-TNFR) family
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