DIFFERENT GROWTH-FACTOR REQUIREMENTS FOR HUMAN TH2 CELLS MAY REFLECT IN-VIVO INDUCED ANERGY

We previously reported the isolation of allergen-specific Th2 lines an d clones from atopy patch test (APT) sites of atopic dermatitis (AD) p atients. Upon stimulation with allergen or anti-CD3 + phorbol myristat e acetate (PMA) IL-4 was released with or without IL-5, while no (or e xtremely low concentrations of) IL-2 and interferon-gamma (IFN-gamma) were detectable. A high IL-4/IFN-gamma ratio facilitates production of allergen-specific IgE, of which high levels are observed in AD patien ts. Here, we show that the above mentioned Th2 cells are notably diffe rent from murine Th2 cells. Not IL-4, which is the autocrine acting gr owth factor for murine Th2 cells, but IL-2 was needed for proliferatio n of these human APT-derived Th2 lines and clones. Of significance, un less exogenous IL-2 was added, no proliferative response to allergen, presented by Epstein-Barr virus-transformed B (EBV-B) cells, non-T cel ls or IgE-bearing Langerhans cells (LC), occurred. Lack of proliferati on and IL-2 production after full T cell receptor (TCR) triggering is a characteristic first described for in vitro anergized T cells. Howev er, like the clones we describe in this study, anergic T cells may ret ain production of cytokines other than IL-2. A further resemblance bet ween anergic T cells and the human Th2 clones reported here is that IL -4 can enhance IL-2-driven proliferation, but is not capable of induci ng T cell growth by itself. The absence of IL-4-driven proliferation d ifferentiates human Th2 cells from murine Th2 cells. Both produce IL-4 when stimulated in a cognate fashion, but only murine Th2 cells will proliferate. We conclude that the presently reported human Th2 cells a re different from murine Th2 cells, in that they need other T cells to produce IL-2 required for their expansion. Moreover, the Th2 cells ph enotypically resemble anergic T cells. As yet, however, we have no clu e as to whether these features account for the current Th2 cells only or for human Th2 cells in general. We hypothesize that the Th2 phenoty pe of AD skin-derived, allergen-specific T cells may be induced in viv o by LC, which lack CD80, and therefore do not provide secondary signa ls through CD28-CD80 interaction.