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

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.

Secretory products from infective forms of Nippostrongylus brasiliensis induce a rapid allergic airway inflammatory response

“…The Th2‐inducing ability of NES has also been used as an adjuvant to induce OVA‐ 20 and hen egg lysozyme‐ 18 specific IL‐4 production by T cells. In addition, NES has been described to suppress IFN‐γ production by rat lymphocytes whilst not effecting IL‐4 or IL‐10 production 21 . The model described in the current manuscript concurs with such observations where we showed that following ex vivo activation, NES‐specific CD4 + T cells produced IL‐4 and IL‐5 but not IFN‐γ.…”

Direct effects of IL-4/IL-13 and the nematode Nippostrongylus brasiliensis on intestinal epithelial cells in vitro

“…Nippostrongylus brasiliensis was maintained in our laboratory by serial passage in SD rats. Nippostrongylus brasiliensis ES product was prepared as described previously (13). Briefly, adult worms were incubated in phosphate‐buffered saline (PBS) (10 000 worms/15 mL) with 100 U/mL of penicillin and 100 μg/mL of streptomycin at 37°C for 24 h. The incubation medium was centrifuged at 20 000 × g for 30 min, and the supernatant was stored at −80°C until use.…”

Up-Regulation of Fas (CD95) and Induction of Apoptosis in Intestinal Epithelial Cells by Nematode - Derived Molecules

“…Alternatively, it may be triggered directly by nematode-derived molecules. N. brasiliensis excretory-secretory product (ES) contains various biologically active molecules, such as acetylcholinesterase, proteases, and a factor that suppresses gamma interferon production (2,4,12,14,20,29). In this context, it is of interest to clarify whether N. brasiliensis ES and/or worm extract (WE) contains factors that induce epithelial cell death.…”