Suppression of Gamma Interferon Transcription and Production by Nematode Excretory-Secretory Antigen during Polyclonal Stimulation of Rat Lymph Node T Cells

Abstract

ABSTRACT Although certain helminth infections preferentially induce type 2 T-cell responses, the immunological mechanisms responsible for type 2 T-cell polarization remain unclear. In the present study, we investigated the effects of excretory-secretory (ES) antigen from the nematode Nippostrongylus brasiliensis on cytokine production by mesenteric lymph node (MLN) cells isolated from naive rats. MLN cells produced considerable levels of gamma interferon (IFN-γ) during a 72-h stimulation with concanavalin A (ConA) or with immobilized anti-CD3 plus soluble anti-CD28 antibodies (anti-CD3/CD28). With either stimulation, 10 μg of ES antigen per ml significantly suppressed IFN-γ and interleukin-2 (IL-2) production without cytotoxic activity. The copresence of anti-IL-4, anti-IL-10, or transforming growth factor β (TGF-β) blocking antibodies did not alter the suppressive effect of ES antigen on IFN-γ production. ES antigen did not affect IL-10 production. Kinetic studies of the effect of ES antigen indicated that the antigen suppressed even ongoing IFN-γ production. Reverse transcription-PCR study showed that in the presence of ES antigen, IFN-γ mRNA expression by MLN cells was suppressed 6 and 12 h after ConA or anti-CD3/CD28 stimulation. ES antigen also significantly suppressed IFN-γ production by purified CD4 + or CD8 + T cells during anti-CD3/CD28 stimulation but did not affect IL-4 production by CD4 + T cells. These findings suggested that the nematode antigen suppressed production of IFN-γ and IL-2 but not IL-4 or IL-10 production. ES antigen-mediated suppression of IFN-γ during the initiation of the immune response may provide a microenvironment that helps generation of type 2 T cells.