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Publication : Pinpointing IL-4-independent acquisition and IL-4-influenced maintenance of Th2 activity by CD4 T cells.

First Author  Cunningham AF Year  2004
Journal  Eur J Immunol Volume  34
Issue  3 Pages  686-694
PubMed ID  14991598 Mgi Jnum  J:115477
Mgi Id  MGI:3691756 Doi  10.1002/eji.200324510
Citation  Cunningham AF, et al. (2004) Pinpointing IL-4-independent acquisition and IL-4-influenced maintenance of Th2 activity by CD4 T cells. Eur J Immunol 34(3):686-94
abstractText  Naive CD4 T cells develop Th2 activity early in primary responses to alum-precipitated proteins by producing IL-4 mRNA and inducing B cells to produce gamma1 and epsilon switch transcripts. Both IL-4-dependent and IL-4-independent pathways for IL-4 induction are recognized, but their relative contribution to the different phases of primary Th2 responses in vivo is uncertain. We show the primary induction of IL-4 synthesis in lymph nodes responding to alum-precipitated protein is overwhelmingly in antigen-specific CD4 T cells and is unimpaired in IL-4Ralpha(-/-) mice, which can produce but do not respond to IL-4 and IL-13. Ig class-switching in extra-follicular responses, reflecting Th2 activity, is also unimpaired in these mice. By contrast, 7 days after immunization--when T cells are selecting B cells in germinal centers and T cell priming has occurred--non-responsiveness to IL-4 is associated with smaller germinal centers, increased levels of T-bet and gamma2a switch transcripts and reduced gamma1 and epsilon transcripts. These data indicate that Th2 characteristics acquired during T cell priming and the initial CD4 T cell interaction with B cells are largely IL-4-independent, whereas IL-4 production induced during priming has a significant role in maintaining the Th2 phenotype as T cells select B cells in germinal centers.
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