International Immunology Advance Access originally published online on January 24, 2005
International Immunology 2005 17(3):269-278; doi:10.1093/intimm/dxh206
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© 2005 The Japanese Society for Immunology
A distinct role for ICOS-mediated co-stimulatory signaling in CD4+ and CD8+ T cell subsets
1 Division of Immunobiology and 2 Department of Flow cytometry Facility, Research Institute for Biological Sciences and 3 Department of Cellular Signaling, Genome and Drug Research Center, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan
4 Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan
Correspondence to: R. Abe; E-mail: rabe{at}rs.noda.tus.ac.jp
While the ligand of inducible co-stimulator (ICOS), B7 homologus protein, is widely expressed in somatic cells, B7-1 and B7-2 expression is mainly limited to lymphoid organs. Thus, the activation of T cells through ICOS without a CD28-mediated signal may occur in physiological situations. In order to gain a better understanding of the role of the ICOS co-stimulatory signal in immune responses, we studied the cellular response of T cells to beads coated with anti-ICOS or anti-CD28, plus sub-optimal anti-CD3 mAb. We demonstrate that while CD28 ligation induced expansion of both CD4+ and CD8+ populations, ICOS ligation only resulted in the expansion of CD8+ T cells, and induced apoptosis in the CD4+ T cell population. It was found that IL-2 is critically required for CD8+ T cell expansion triggered by ICOS ligation, whereas it had only a limited effect on the expansion of CD4+ T cells. This distinct reactivity of CD4+ and CD8+ T cell populations to exogenous IL-2 strongly correlates with the expression level of IL-2 receptor ß-chain, CD122, on T cells. Furthermore, we defined a small but distinct population of memory phenotype CD4+ T cells that constitutively express ICOS. Interestingly, while naive CD4+ T cells were unable to produce IL-2, ICOS-expressing T cells produced a substantial amount of IL-2 by stimulation with anti-ICOS/CD3 beads, suggesting that IL-2, which is indispensable for CD8+ T cell expansion, is produced by this ICOS-expressing T cell population. These results provide evidence indicating that the ICOS co-stimulatory signal plays a distinct role in the development of CD4+ and CD8+ T cell-mediated immune responses.
Keywords: CD4/CD8 T cell, co-stimulation, cytokine, ICOS
Transmitting editor: K. Yamamoto
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