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
Autor: | Patrice Hermann, Yuetsu Tanaka, Yusei Ohshima, Liang Peng Yang, Guy Delespesse, Martin Sergerie, Peter R. Baum, Takashki Uchiyama |
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Rok vydání: | 1998 |
Předmět: |
CD4-Positive T-Lymphocytes
CD3 Complex Cellular differentiation medicine.medical_treatment Immunology Priming (immunology) OX40 Ligand Biology Biochemistry Receptors Tumor Necrosis Factor Th2 Cells CD28 Antigens medicine Humans RNA Messenger education Interleukin 5 Cells Cultured Interleukin 4 education.field_of_study Interleukin-13 Membrane Glycoproteins CD28 Cell Differentiation Dendritic Cells Cell Biology Hematology Receptors OX40 Fetal Blood Interleukin-12 Tumor Necrosis Factor Receptor Superfamily Member 7 Cell biology OX40 ligand Cytokine Gene Expression Regulation Interleukin 13 Interleukin-4 Interleukin-5 Muromonab-CD3 |
Zdroj: | Blood. 92:3338-3345 |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood.v92.9.3338.421k19_3338_3345 |
Popis: | 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. |
Databáze: | OpenAIRE |
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