A distinct role for ICOS-mediated co-stimulatory signaling in CD4+ and CD8+ T cell subsets.
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.
Watanabe
Masashi
M
Division of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Hara
Yasushi
Y
Tanabe
Kazunari
K
Toma
Hiroshi
H
Abe
Ryo
R
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D015375:Receptors, Interleukin-2