Modulation of the Functions of Dengue Virus-Specific Human CD8⁺Cytotoxic T Cell Clone by IL-2, IL-7 and IFNγ

Abstract

Lymphokines play an important role in immune responses to viruses by modulating functions of T lymphocytes. In the present study, we examined the effects of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-7 (IL-7), and interferon gamma (IFN gamma) on proliferation, cytotoxic activity and lymphokine production of a dengue virus-specific CD8+ human cytotoxic T lymphocyte (CTL) clone. IL-2 and IL-7 induced proliferation of the CD8+ CTL clone in the presence or absence of specific antigen, while IFN gamma suppressed proliferation of the clone. IL-7 and IFN gamma augmented dengue virus-specific cytotoxic activity without inducing non-specific cytotoxic activity, and IL-2 induced non-specific cytotoxic activity. IL-2 induced IFN gamma production by the CD8+ CTL clone. IL-4 and IL-6 did not modulate the functions of the CD8+ CTL clone in these experimental conditions. These results suggest that functions of dengue virus-specific CD8+ CTL are modulated by IL-2, IL-7 and IFN gamma, and that IL-7 is a lymphokine useful to induce growth and to maintain specific cytotoxic activity of CD8+ CTL clones in vitro.

Functional profile of human influenza virus-specific cytotoxic T lymphocyte activity is influenced by interleukin-2 concentration and epitope specificity

“…In humans, only CTL clones or T cell lines, passaged multiple times in vitro , have been studied. Increased IFN‐γ production and lysis by human dengue virus‐specific CTL clones cultured under IL‐2 hi conditions were observed [37]. Also, it has been found more recently that IL‐2 had a positive effect on influenza A virus epitope (M1 58−66 )‐specific CTL that had been stimulated three times with peptide‐pulsed APC before their functional properties were investigated [36].…”

“…High IL‐2 concentrations during effector cell differentiation resulted in highly efficient CTL, while effector cell differentiation in IL‐2 lo conditions resulted in CTL less efficient in mobilizing CD107a and producing IFN‐γ and TNF‐α. The effect of IL‐2 on effector cell function of CTL has been reported previously for T cells from humans, monkeys and mice [26,34–38]. In humans, only CTL clones or T cell lines, passaged multiple times in vitro , have been studied.…”

Understanding the contribution of cellular immunity to dengue disease pathogenesis

“…T-cell recognition of DENV proteins DENV-specific CD4 1 and CD8 1 T-cell epitopes have been identified on multiple proteins of DENV (39)(40)(41)(42)(43)(44). While T-cell epitopes have been identified on the structural proteins, the vast majority of T-cell epitopes have been found on nonstructural proteins ( Table 1).…”

New Mouse Model for Dengue Virus Vaccine Testing

“…They probably play an important role in controlling both primary (14,15,17,21) and secondary (30) infections. It has also been suggested that IFN-␥ plays a role in modulating DEN virus-specific CD8 ϩ CTL functions (19). Children with DEN fever and DHF produce detectable levels of IFN-␣.…”