Interleukin-7 modulates intracytoplasmatic CD23 production and induces adhesion molecule expression and adhesiveness in activated CD4+CD23+ T cell subsets.
The low-affinity receptor for IgE, CD23, has been described in several pathological conditions. However, the factors involved in the upregulation or downregulation of this receptor are still debated. We studied the effect of interleukin 7 (IL-7) on the production of CD23 in normal PBT cells stimulated with PMA + Ca2. The results demonstrate that cytoplasmic CD23 level was significantly augmented by costimulation with PMA + Ca2 plus IL-7 (1000 U/ml). Using an intracytoplamatic cytometric analysis, an accumulation of intracellular CD23 was observed at 48 hr in the presence of IL-7. This appears to have a profile different from the CD23 surface expression peaking at 72 hr of culture. We were also able to show that sCD23 was specifically increased by IL-7 and occurred with an early peak at 72 hr and a late peak at 120 hr of culture. The increased release and the biphasic production of sCD23 may reside in an accelerated degradation of the receptor due to an excessive accumulation of it. Restimulation of CD4+ T cells with PMA + Ca2 without IL-7 changed the profile of sCD23 production showing a second peak at 144 hr of culture. The induction of IL-7 on CD23 production appears to be independent of IL-2, IL-4, IL-9, and IL-15. Indeed, the addition of specific mAbs anti-IL-2, -IL-4, -IL-9, -IL-15, or anti-IL-2R was unable to block the effect of IL-7 on CD23. The addition of IL-7 to specific subset CD4+CD23+ was able to augment the adhesiveness of T cells to parenchymal cell monolayers. The use of different cytokine (IL-2, IL-4, IL-9, IL-15) resulted in no increase of adhesiveness. In contrast, the addition of IL-7 to a different T cell subset (i.e., CD4+CD23-) was unable to rescue the lack of adhesiveness observed in these cells. The adhesion molecules LFA-1 and VLA-4 were responsible for the augmented adhesiveness of activated CD4+CD23+ T cells cultured in the presence of IL-7. Blocking experiments with anti-LFA-1beta, VLA-4alpha, anti-LFA-1beta plus VLA-4alpha mAbs, or anti-ICAM-1 mAb added to the monolayers resulted in a complete inhibition of adhesion to parenchymal monolayers. In contrast, the addition of anti-IL-7 or anti-IL-7R mAbs was able to block the augmented adhesiveness of CD4+CD23+ cells to monolayers observed in the presence of IL-7. A significant augmentation of LFA-1 and VLA-4 was observed in cells cultured in the presence of IL-7. Taken together these findings point to the likelihood that IL-7 is responsible for the observed quantitative difference in the level of adhesion molecules and may open a new role of CD23 in the immune regulations.
Fratazzi
C
C
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Carini
C
C
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000187:drug effects*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D008213:Lymphocyte Activation; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000187:drug effects*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D015851:Interleukin-7; D007378:Interleukins; D017455:Receptors, IgE; D013755:Tetradecanoylphorbol Acetate