Requirement of the IFN-alpha/beta-induced CXCR3 chemokine signalling for CD8+ T cell activation.
BACKGROUND
Activation of both CD4+ T and CD8+ T cells is triggered by the engagement of the T cell antigen receptor (TCR) with MHC/peptide complexes on antigen-presenting cells. This process also requires other molecular interactions, which transmit co-stimulatory signals to these T cells. To ensure an effective immune response, distinct T cell subsets may additionally employ unique mechanism(s) for efficient activation.


RESULTS
We here show that mutant CD8+ T cells lacking the IFN-alpha/beta signalling components are hyporesponsive to antigen stimulation in vitro. We further show that IFN-alpha/beta-mediated signals are required for induction of the chemokines IP-10/I-TAC and their common receptor, CXCR3, and in turn provide evidence that CXCR3-mediated signals indeed function in the activation and proliferation of CD8+ T cells, particularly for the CD44low naive phenotype cells.


CONCLUSIONS
The CXCR3 chemokine system is regulated by IFN-alpha/beta in CD8+ T cells, and it is critical for the efficient cell activation. The present study therefore reveals a novel role of the IFN-alpha/beta-CXCR3 signalling cascade in CD8+ T cell activation.
Ogasawara
Kouetsu
K
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Hida
Shigeaki
S
Weng
Youmin
Y
Saiura
Akio
A
Sato
Kojiro
K
Takayanagi
Hiroshi
H
Sakaguchi
Shinya
S
Yokochi
Taeko
T
Kodama
Tatsuhiko
T
Naitoh
Makoto
M
De Martino
Julie A
JA
Taniguchi
Tadatsugu
T
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D016898:Interferon-alpha; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000276:immunology* / Q000502:physiology
C515188:Cxcr3 protein, mouse; D007370:Interferon Type I; D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; C076799:interferon-alpha 8