Naïve CD4+ T cells from patients with atopic dermatitis show an aberrant maturation towards IL-4-producing skin-homing CLA+ cells.
Overproduction of interleukin-4 (IL-4) has been reported in lesional and in peripheral T cells from patients with atopic dermatitis (AD). It is not clear whether the development of IL-4-producing T helper type 2 (Th2) cells from naïve precursors is an intrinsic phenomenon of T cells or whether other, extrinsic factors play a significant role. To analyze these alternatives, we investigated the IL-4 production of effector T cells generated in vitro from highly purified CD4+ CD45RA+ naïve T cells in the absence of signals derived from antigen-presenting cells. Effector T cells generated from naïve precursors from both AD and healthy donors produced comparable amounts of IL-4 after restimulation. Priming in the presence of exogenous IL-4 enhanced the production of IL-4 while neutralizing endogenously produced IL-4 abolished IL-4 production similarly in atopic and healthy T cells. A subset of effector T cells acquired the expression of the cutaneous lymphocyte antigen (CLA). The frequency of CLA+ T cells was not different between atopic and healthy donors. CLA+ T cells, differentiated from naïve atopic, but not healthy T cells, showed a preferential Th2 cytokine profile as assessed by intracellular cytokine staining. Also effector T cells derived from atopic patients without dermatitis tended to show this imbalance, although it was not significantly different to healthy controls. This Th2 cytokine profile did not develop when naïve T cells were cultured in the presence of IL-12. In conclusion, high IL-4 production in developing T cells from AD patients was associated with CLA expression, the net IL-4 production of all effector CD4+ T cells, however, was similar to IL-4 production by T cells from healthy donors.
Jung
T
T
Department of Dermatology, University Göttingen, Göttingen, Germany. Thomas.Jung@Pharma.Novartis.Com
Moessner
R
R
Neumann
C
C
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D008875:Middle Aged; D012867:Skin / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma