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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3338-3345
OX40 Costimulation Enhances Interleukin-4 (IL-4) Expression at
Priming and Promotes the Differentiation of Naive Human
CD4+ T Cells Into High IL-4-Producing Effectors
Yusei Ohshima,
Liang-Peng Yang,
Takashi Uchiyama,
Yuetsu Tanaka,
Peter Baum,
Martin Sergerie,
Patrice Hermann, and
Guy Delespesse
From the University of Montreal, Centre de Recherche Louis-Charles
Simard, Notre-Dame Hospital, and the Department of Obstetrics and
Gynecology, Montreal, Quebec, Canada; the Institute for Virus Research,
Kyoto University, Kyoto, Japan; Kitasato University, Kitasato,
Sagamihara, Kanagawa, Japan; and Immunex Research and Development Corp,
Seattle, WA.
Th2 cell development is critically dependent on the presence of
interleukin-4 (IL-4) at priming. The cellular origin and the mechanisms
regulating this early production of IL-4 at the site of naive T-cell
priming are extensively investigated. We previously reported that
anti-CD3-activated and CD28-costimulated naive human CD4+ T cells themselves release very low but sufficient
levels of IL-4 to support their development into high IL-4-producing
cells. We show here that ligation of OX40 Ag, a member of the tumor
necrosis factor receptor (TNF-R) family, on activated
umbilical cord blood CD4+ T cells upregulates IL-4
production at priming and thereby promotes their development into
effector cells producing high levels of the type 2 cytokines IL-4,
IL-5, and IL-13. OX40 ligation increases four times the expression of
IL-4 mRNA after 48 hours of anti-CD3/B7.1 activation and significantly
augments the release of IL-4 and IL-13 in primary cultures. The effects
of OX40 costimulation on Th cell differentiation are observed in the
presence of optimal and suboptimal CD28 stimulation. Because OX40
ligand is expressed on dendritic cells, the OX40 costimulation pathway
may be involved in the physiological regulation of Th cell development
by augmenting the differentiation of IL-4-producing cells.
© 1998 by The American Society of Hematology.
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