Establishment of memory for IL-10 expression in developing T helper 2 cells requires repetitive IL-4 costimulation and does not impair proliferation.
T helper (Th) lymphocytes can develop memory for the expression of particular cytokines, like IL-4 or IL-10, in that reexpression of those cytokines is independent of the original costimulatory signal IL-4 and depends only on T cell receptor stimulation. Here, we show that in the course of Th2 cell differentiation in vitro, IL-4 memory is established during primary activation of naïve Th cells, whereas the establishment of IL-10 memory requires repetitive stimulation of the Th cell with IL-4 and T cell receptor. Likewise, established IL-10 memory, maintained in the absence of further IL-4 signals, was observed in individual IL-10-producing cells generated from in vivo antigen-experienced CD62L(low) Th cells and isolated by using the newly developed cytometric cytokine secretion assay for IL-10. In naïve Th cells undergoing primary activation, the induction of both IL-4 and IL-10 memory requires DNA synthesis, but reexpression of the cytokine genes can occur throughout cell cycle. In in vitro polarized Th2 cell populations, Th cells with IL-4 or IL-10 memory do not differ in proliferative behavior. Populations of Th cells isolated from polarized Th2 cultures according to expression of IL-4 or IL-10 also do not differ in proliferative behavior. Their proliferation mainly depends on IL-2. Thus, effector memory Th lymphocytes with memory for IL-4 or IL-10 expression are not intrinsically impaired in their proliferative potential and can play an essential role in reactive immunological memory and its regulation.
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D002453:Cell Cycle; D002454:Cell Differentiation; D002469:Cell Separation; D004247:DNA / Q000096:biosynthesis; D007156:Immunologic Memory; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; C111390:OVA 323-339; D010446:Peptide Fragments; D016753:Interleukin-10; D015847:Interleukin-4; D010047:Ovalbumin; D004247:DNA