title: Antigen-specific CD4+ effector T cells: analysis of factors regulating clonal expansion and cytokine production: clonal expansion and cytokine production by CD4+ effector T cells.
abstract: In order to fully understand T cell-mediated immunity, the mechanisms that regulate clonal expansion and cytokine production by CD4(+) antigen-specific effector T cells in response to a wide range of antigenic stimulation needs clarification. For this purpose, panels of antigen-specific CD4(+) T cell clones with different thresholds for antigen-induced proliferation were generated by repeated stimulation with high- or low-dose antigen. Differences in antigen sensitivities did not correlate with expression of TCR, CD4, adhesion or costimulatory molecules. There was no significant difference in antigen-dependent cytokine production by TG40 cells transfected with TCR obtained from either high- or low-dose-responding T cell clones, suggesting that the affinity of TCRs for their ligands is not primary determinant of T cell antigen reactivity. The proliferative responses of all T cell clones to both peptide stimulation and to TCRbeta crosslinking revealed parallel dose-response curves. These results suggest that the TCR signal strength of effector T cells and threshold of antigen reactivity is determined by an intrinsic property, such as the TCR signalosome and/or intracellular signaling machinery. Finally, the antigen responses of high- and low-peptide-responding T cell clones reveal that clonal expansion and cytokine production of effector T cells occur independently of antigen concentration. Based on these results, the mechanisms underlying selection of high "avidity" effector and memory T cells in response to pathogen are discussed.
authors.affiliation: Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Ohnuki
authors.forename: Yuri
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Sakiko
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Shiho
authors.initials: S
authors.lastname: Watanabe
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ogawa
authors.forename: Motoko
authors.initials: M
authors.lastname: Kotani
authors.forename: Haruo
authors.initials: H
authors.lastname: Kozono
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
authors.forename: Ryo
authors.initials: R
authors.lastname: Abe