Expression of functional selectin ligands on Th cells is differentially regulated by IL-12 and IL-4

Immune responses may be qualitatively distinct depending on whether Th1 or Th2 cells predominate at the site of Ag exposure. T cell subset-specific ex pression of ligands for vascular selectins may underlie the distinct patter ns of recruitment of Th1 or Th2 cells to peripheral inflammatory sites. Her e we examine the regulation of selectin ligand expression during murine T h elper cell differentiation. Large numbers of Th1 cells interacted with E- a nd P-selectin under defined flow conditions, while few Th2 and no naive T c ells interacted, Th1 cells also expressed more fucosyltransferase VII mRNA than naive or Th2 cells. IL-12 induced expression of P-selectin ligands on Ag-activated naive T cells, even in the presence of IL-4, and on establishe d Th2 cells restimulated in the presence of IL-12 and IFN-gamma, In contras t, Ag stimulation alone induced only E-selectin ligand, Interestingly, rest imulation of established Th2 cells in the presence of IL-12 and IFN-gamma i nduced expression of P-selectin ligands but not E-selectin ligands; IFN-gam ma alone did not enhance expression of either selectin ligand, In summary, functional P- and E-selectin ligands are expressed on most Th1 cells, few T h2 cells, but not naive T cells. Furthermore, selectin ligand expression is regulated by the cytokine milieu during T cell differentiation. IL-12 indu ces P-selectin ligand, while IL-4 plays a dominant role in down-regulating E-selectin ligand.