OX40 (CD134) and OX40 ligand interaction plays an adjuvant role during in vivo Th2 responses

The role of OX40‐OX40 ligand (OX40L) interaction in Th cell differentiation remains contentious. In vitro studies have revealed a Th2‐biased effect by OX40 signals in T cells. However, in vivo studies demonstrated that OX40‐OX40L interaction is involved in responses either Th1 or Th2, or both, which...

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Published in:European journal of immunology 2003-09, Vol.33 (9), p.2372-2381
Main Authors: Ishii, Naoto, Ndhlovu, Lishomwa C., Murata, Kazuko, Sato, Takayuki, Kamanaka, Masahito, Sugamura, Kazuo
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antigens - immunology
Antigens, Differentiation - metabolism
Costimulatory signal
Leishmania major
Leishmania major - immunology
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
OX40 ligand
Th2 Cells - immunology
Th2 Cells - metabolism
Th2 response
Tumor Necrosis Factors
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Summary:The role of OX40‐OX40 ligand (OX40L) interaction in Th cell differentiation remains contentious. In vitro studies have revealed a Th2‐biased effect by OX40 signals in T cells. However, in vivo studies demonstrated that OX40‐OX40L interaction is involved in responses either Th1 or Th2, or both, which appears to be dependent on the experimental conditions used. We document in our report Th cell differentiation in OX40L‐deficient and OX40L‐transgenic (Tg) mice in response to protein antigens (Ag) and to Leishmania major (L. major) infection. Upon immunization with protein Ag, we demonstrate the adjuvant effect of OX40 signals during in vivo Th2 responses. However, adjuvant treatment to mice ameliorates the Th2‐specific effect of OX40‐OX40L interaction and rather induces concurrent promotion of both Th1 and Th2 responses via OX40 signals. Thus, previous reports showing promotion of Th1 response by OX40‐OX40L interaction may in actual fact be affected by the adjuvant effects mediated by the various experimental conditions. Indeed, constitutive OX40–OX40L interactions in OX40L‐Tg mice converted the normally resistant C57BL/6 strain, into a susceptible status following L. major infection due to an extraordinary elevated Th2 response. These results provide convincing evidence demonstrating that the OX40‐OX40L interaction is paramount in the development of Th2 responses in vivo.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200324031