A stimulating paper from Mohrs and colleagues that shows that IL-4 and IFN-g signaling during Heligmosomoides polygyrus or Toxoplasma gondii respectively, is: i) widespread throughout the LN, ii) independent of direct cell contact and, iii) is not a limiting factor in B cell maturation or helper T cell differentiation. These results are challenging in view of our own data that show that during LN responses to alum-precipitated protein antigens IL-4 is dispensable for the early induction, but not for the maintenance, of Th2-features including B cell maturation or helper T cell differentiation more. In addition, previous work from our laboratory has shown that Th1 and Th2 characteristics start to develop during T cell priming to alum-precipitated protein mixed with killed Bordetella pertussis. This suggests that cytokines in these circumstances do not act globally in the LN, and that Th2 response to hapten-protein can proceed in a node where there is substantial Th1 activity.
Thus, even though IL-4 induces STAT6 phosphorylation in the vast majority of CD19+, CD4+ and CD8+ cells it may not be required for the early induction of Th2 features in vivo. Having said this it may be dangerous to compare responses elicited with alum-precipitated proteins with responses to H. polygyrus infection. Further studies are warranted to fully understand the role and impact of IL-4 on the LN microenvironment.