Differential regulation of VLA-2 expression on Th1 and Th2 cells: a novel marker for the classification of Th subsets.

Abstract

We found that T(h)1 cells derived from ovalbumin (OVA)-specific TCR transgenic (DO11.10) mice showed significantly higher levels of VLA-2 (CD49b/CD29) expression than T(h)2 cells. In the early days (until 6 days) during induction of T(h)1 or T(h)2 cells, the expression of VLA-2 was gradually increased on both T(h) subsets. Thereafter, VLA-2 expression was further up-regulated on T(h)1 cells until 13 days, while a significant decrease of VLA-2 was observed in T(h)2 cells, resulting in a marked difference of expression at day 13. Up-regulation of VLA-2 on T(h)1 cells was not impaired in IFN-gamma(-/-) T(h) cells nor blocked by anti-IL-12 mAb treatment on wild-type T(h) cells, suggesting that up-regulation of VLA-2 on T(h)1 cells occurs in an IFN-gamma- and IL-12-independent manner. In contrast, T(h) cells cultured under IL-4-depleted T(h)2 conditions abrogated the down-regulation of VLA-2 expression, suggesting that down-regulation of VLA-2 expression on T(h)2 cells was dependent on IL-4. The finding that STAT6(-/-) T(h)2 cells did not show any down-regulation of VLA-2 expression and expressed the same levels of VLA-2 as T(h)1 cells indicated a critical role for the IL-4 receptor/STAT6 signaling pathway in IL-4-dependent down-regulation of VLA-2 on T(h)2 cells. Stimulation of T(h)1 cells by VLA-2 ligands such as collagen type I or agonistic mAb provided co-stimulation for anti-CD3 mAb-induced IFN-gamma production. However, these ligations had little effect on the IL-4 production of T(h)2 cells. Together, these results indicate that VLA-2 is a novel functional marker that dissociates T(h)1 from T(h)2 cells, and thus might be useful for therapeutic monitoring of T(h)1-dependent immune diseases such as rheumatoid arthritis or Crohn's disease.

• Authors: Kotaro Sasaki, Takemasa Tsuji, Takafumi Jinushi, Jyunko Matsuzaki, Takeshi Sato, Kenji Chamoto, Yuji Togashi, Toshiaki Koda, Takashi Nishimura
• Journal: International immunology (Int Immunol) Vol. 15 Issue 6 Pg. 701-10 (Jun 2003) ISSN: 0953-8178 [Print] England
• PMID: 12750354 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Integrin alpha2beta1
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Animals, Genetically Modified
• Biomarkers
• Female
• Flow Cytometry
• Gene Expression Regulation (drug effects, immunology)
• Integrin alpha2beta1 (biosynthesis, drug effects)
• Interferon-gamma (biosynthesis, pharmacology)
• Interleukin-4 (biosynthesis, pharmacology)
• Mice
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocyte Subsets (classification, drug effects, metabolism)
• T-Lymphocytes, Helper-Inducer (classification, drug effects, metabolism)