RESUMO
Type 2 cytokines, such as interleukin-4 (IL-4) and IL-13, are associated with immunoglobulin E (IgE) production. This association has also been observed in CD8+ T cells from patients infected with leprosy and human immunodeficiency virus (HIV). Using intracellular cytokine staining and flow cytometry, the cytokine profile [IL-2, IL-4, IL-10, IL-13, and interferon (IFN)-gamma] of both CD4+ and CD8+ memory/effector T cells circulating in atopic dermatitis (AD) patients was investigated at the single cell level. The levels of type 2 cytokines in CD4+ T cells or CD8+ T cells in AD patients with high levels of serum IgE (AD-H), low levels of serum IgE (AD-L), and healthy controls were compared. Increased production of IL-4 and IL-13 in both CD4+ CD45RO+ T cells and CD8+ CD45RO+ T cells after 4 h in vitro stimulation with phorbol 12-myristate 13-acetate and ionomycin, was more prominent in AD-H patients than in AD-L patients or healthy controls, whereas IFN-gamma-producing CD4+ CD45RO+ T cells and CD8+ CD45RO+ T cells were relatively diminished in AD-H patients. CD4+ T cells and CD8 + T cells from AD-H patients, cultured for 48 h with phorbol 12-myristate 13-acetate and ionomycin, released larger amounts of IL-4 and IL-13 but smaller amounts of IFN-gamma than both types of cells from AD-L patients or healthy controls. In addition, when stimulated with immobilized anti-CD3 monoclonal antibody (MoAb) and anti-CD28 MoAb, CD4+ CD45RO+ T cells and CD8+ CD45RO+ T cells from AD-H patients contained more IL-4-producing cells but fewer IFN-gamma-producing cells compared with healthy controls. Finally, spontaneous mRNA expression of IL-4 in blood CD8+ CD45RO+ T cells isolated from AD-H patients was increased, as determined by reverse transcriptase-polymerase chain reaction. Therefore, in AD patients with high IgE levels, type 2 cytokine (IL-4 and IL-13) expression is associated with IgE production, in both CD4+ CD45RO+ T cell and CD8+ CD45RO+ T cell subsets.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Dermatite Atópica/sangue , Imunoglobulina E/sangue , Interleucina-13/biossíntese , Interleucina-4/biossíntese , Adolescente , Adulto , Circulação Sanguínea/imunologia , Células Cultivadas , Criança , Feminino , Citometria de Fluxo , Humanos , Interferon gama/sangue , Interferon gama/metabolismo , Interleucina-13/sangue , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , RNA Mensageiro/metabolismoRESUMO
In an earlier study, we generated a large number of Mycobacterium leprae-responsive and M. leprae-nonresponsive T cell clones (TCC) from the lesional skin of immunologic unstable borderline leprosy patients. In that study, we divided TCC into type 1- and type 2-like on the basis of their IFN-gamma and IL-4 expression. To explore whether other cytokines are coproduced along with IFN-gamma and IL-4, we investigated the secretion of a panel of other cytokines (TNF-alpha, IL-5, IL-6, IL-10, and IL-13) by a large number of these TCC. Upon analysis of 139 M. leprae-responsive TCC, we observed a positive correlation in the coproduction of IFN-gamma/TNF-alpha (r = 0.81), and in that of IL-4/IL-5 (r = 0.83), IL-4/IL-13 (r = 0.80), and IL-5/IL-13 (r = 0.82). Polarized type 1-like TCC produced dominantly IFN-gamma/TNF-alpha, and polarized type 2-like TCC predominantly IL-4/IL-5/IL-13. Most type 0-like TCC produced both sets of cytokines. In contrast, type 1- and type 2-like subsets of M. leprae-nonresponsive TCC (n = 58) did not show the same coexpression of these cytokines. Furthermore, when the differential expression of a broad panel of cytokines by individual M. leprae-responsive TCC is considered, it appeared that additional phenotypes could be recognized. These results suggested that distinct isotypes of type 1- and type 2-like T cells, based on the secretion of a panel of cytokines, may reflect M. leprae-specific characteristics.