Blood, Vol. 89 No. 3 (February 1), 1997:
pp. 1110-1110
CORRESPONDENCE
Interferon-
Upregulates Both Interleukin-10 and Interferon-
Production by Human CD4+ T Cells
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LETTER |
To the Editor:
Aman et al1 recently reported that interferon-
(IFN-) upregulates the production of interleukin-10 (IL-10) by activated monocytes or CD4+ T cells. These data are in line with our previously published findings2 which showed that IFN- downregulates IL-5 production by human CD4+ T cells while it significantly increases IL-10 secretion. These effects of IFN- were observed both on resting CD4+ T cells from normal individuals and on differentiated Th2-like cells isolated from patients with the hypereosinophilic syndrome (HES).
Although upregulation of IL-10 secretion might indeed contribute to some antiinflammatory properties of IFN-, we would like to underline that IFN- also upregulates the synthesis of IFN-
, a well-known proinflammatory cytokine. Firstly, it has been well established that, when present in the induction phase of the immune response, IFN- favors the differentiation of CD4+ T cells into Th1 cells.3 Secondly, we found that IFN- directly upregulates the production of IFN- by CD4+ T cells. As shown in Fig 1, IFN- stimulates in a dose-dependent manner the production of both IL-10 and IFN- by resting CD4+ T cells activated either by phorbol myristate acetate (PMA) and anti-CD28 monoclonal antibody (MoAb) or anti-CD3 MoAb cross-linked on fibroblasts transfected with the B7-1. gene.
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| Fig 1.
Effects of recombinant IFN- on the production of IL-10 and IFN- by CD4+ T cells. Graded doses of recombinant IFN- (Schering-Plough, Innishannon, Ireland) were added to CD4+ T cells purified from peripheral blood of five healthy volunteers and stimulated with either PMA (1 ng/mL) and anti-CD28 MoAb (1 µg/mL) ( ), or the CLB-T3/4.1 anti-CD3 MoAb (100 ng/mL) cross-linked on fibroblasts transfected with the B7-1 gene ( ), as previously described.2 After 48 hours, culture supernatants were harvested for determination of immunoreactive IL-10 and IFN- by ELISA, as previously described.2 Data are shown as mean ± SEM.
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Interestingly, IL-12 like IFN- also promotes both IFN- and IL-10 synthesis.4 This parallel induction of IFN- and IL-10 might be important for the natural regulation of immune responses. Moreover, it could be relevant to the therapeutic applications of IFN-, especially in HES. Indeed, we found that IFN- increased IFN- production by in vivo differentiated CD4+CD3- Th2 clones isolated from two patients with HES. As IFN- inhibits differentiation of eosinophils and their recruitment into tissue,5,6 we suggest that the beneficial effects of IFN- in this condition7 might be related not only to inhibition of IL-5 and upregulation of IL-10 synthesis but also to IFN- upregulation.
Liliane Schandené
Elie Cogan
Alain Crusiaux
Michel Goldman
Departments of Immunology and Internal Medicine Hôpital Erasme Université Libre de Bruxelles Brussels, Belgium
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REFERENCES |
1.
Aman JA,
Tretter T,
Eisenbeis I,
Bug G,
Decker T,
Aulitzky WE,
Tilg H,
Huber C,
Peschel C:
Interferon- stimulates production of interleukin-10 in activated CD4+ T cells and monocytes.
Blood
87:4731,
1996[Abstract/Free Full Text]
2.
Schandené L,
Del Prete GF,
Cogan E,
Stordeur P,
Crusiaux A,
Kennes B,
Romagnani S,
Goldman M:
Recombinant Interferon-alpha selectively inhibits the production of interleukin-5 by human CD4+ T cells.
J Clin Invest
97:309,
1996[Medline]
[Order article via Infotrieve]
3.
Parronchi P,
De Carli M,
Manetti R,
Simonelli C,
Sampognaro S,
Piccinni MP,
Macchia D,
Maggi E,
Del Prete G,
Romagnani S:
IL-4 and IFN ( and ) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones.
J Immunol
149:2977,
1992[Abstract]
4.
Jeannin P,
Delneste Y,
Seveso M,
Life P,
Bonnefoy JY:
IL-12 synergizes with IL-2 and other stimuli in inducing IL-10 production by human T cells.
J Immunol
156:3159,
1996[Abstract]
5.
Ochiai K,
Iwamoto I,
Takahashi H,
Yoshida S,
Tomioka H,
Yoshifda S:
Effect of IL-4 and interferon-gamma (IFN-gamma) on IL-3 and IL-5-induced eosinophil differentiation from human cord blood mononuclear cells.
Clin Exp Immunol
99:124,
1995[Medline]
[Order article via Infotrieve]
6.
Iwamoto I,
Nakajima H,
Endo H,
Yoshida S:
Interferon- regulates antigen-induced eosinophil recruitement into the mouse airways by inhibiting the infiltration of CD4+ T cells.
J Exp Med
177:573,
1993[Abstract/Free Full Text]
7.
Cogan E,
Schandené L,
Crusiaux A,
Cochaux P,
Velu T,
Goldman M:
Clonal proliferation of type 2 helper T cells in a man with the hypereosinophilic syndrome.
N Engl J Med
330:535,
1994[Free Full Text]
