A distinct role for ICOS-mediated co-stimulatory signaling in CD4+ and CD8+ T cell subsets

Int Immunol. 2005 Mar;17(3):269-78. doi: 10.1093/intimm/dxh206. Epub 2005 Jan 24.


While the ligand of inducible co-stimulator (ICOS), B7 homologous 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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Inducible T-Cell Co-Stimulator Protein
  • Lymphocyte Activation
  • Mice
  • Receptors, Interleukin-2 / metabolism
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology*


  • Antigens, Differentiation, T-Lymphocyte
  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Protein
  • Receptors, Interleukin-2