Intracellular production of IL-2, IL-4, IFN-γ, and TNF-α by peripheral blood CD3+ and CD4+ T cells in children with atopic dermatitis

Abstract

The role of the type-2 T helper (Th2) cell-mediated immune response in the immunopathogenesis of atopic dermatitis (AD) is well documented. Whether polarized immunoresponse is confined to antigen-specific T cells or is distributed among all T cell subsets is still controversial. We investigated frequencies of interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) producing CD3(+) and CD4(+) T cells in peripheral blood from children with atopic dermatitis and healthy subjects with and without in vitro stimulation. Children with severe AD had a significantly lower percentage of CD4(+) T cells spontaneously expressing IL-4 compared with healthy controls (p <0.01). Polyclonal stimulation significantly increased cytokine production in both AD patients and healthy individuals. Frequencies of CD3(+) and CD4(+) producing IL-2, IL-4, IFN-gamma, and TNF-alpha after in vitro stimulation with phorbol-12-myristate 13-acetate (PMA) + ionomycin were comparable in the AD and control groups. In response to PMA/ionomycin, children with AD and asthma symptoms had a significantly lower percentage of CD3(+) T cells producing TNF-alpha. We failed to demonstrate evidence of an imbalance with respect to type-2 cytokine productions in children with AD. Comparable induction of Th1 and Th2 cytokines in polyclonally stimulated peripheral CD3(+) and CD4(+)T cells from AD patients and controls puts into question the polarized Th2 immune response as a general characteristic of T cells in children with atopic dermatitis.

Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population

“…Early ICS studies fairly consistently detected expansion of T H 2 T cells 7,8,13,14,24,25 and decreased T H 1 cell frequencies in patients with AD versus control subjects. 7,8,13,[24][25][26] The more newly recognized T-cell subsets in patients with AD have been poorly characterized in blood; 2 studies in Japanese patients detected an expansion of T H 17 T-cell frequencies in blood of patients with severe disease, 27,28 and differences in IL-22-producing T-cell frequencies were detected in blood from patients with AD compared with those with psoriasis, but no studies have measured expression compared with that in healthy control subjects.…”

“…[7][8][9][10][11][12][13][14][15] Furthermore, most of these studies were done before human T H 9, T H 17, and T H 22 T-cell populations were characterized.…”

Expression of CD3, CD4, CD8, CD21, and MHC II lymphocyte antigens and serum IL-10 concentration in dogs with atopic dermatitis complicated by purulent dermatitis

“…CD4 lymphocytes, which, together with "professional" APC antigen presenting cells, play a central role in the immunoregulation, identify epitopes targeted by the immune response. In response to the antigen, the differentiation of CD4 T cells toward the Th1 profile, which produces IL-2, IL-12, TNF, IFN, or Th2 producing IL-4, IL-5, IL-10, and IL-13 takes place (5,9,10,17,18). Both T-cell subsets have CD4 surface molecules and recognise the antigen presented in association with MHC class II molecules (5).…”

“…Interleukin 10 (IL-10), known as an immunosuppressive and antiinflammatory cytokine, is produced primarily by Th2 lymphocytes, but also by B lymphocytes, monocytes, macrophages, and keratynocytes. Its activity inhibits the synthesis of inflammatory cytokines, reduces the molecular expression of MHC class II antigens on APC, inhibits the formation of Th1 cells, and stimulates "directed" B cells to switch to IgE synthesis (10,19). It is believed that the Th2 immunological response is controlled by CD4+CD25+ T regulatory lymphocytes (Treg) and regulatory T cells type 1 able to release IL-10 (1).…”

Cytokines and other immunological biomarkers in children's environmental health studies

“…However, these associations of Th1/Th2 are not consistent for all allergic disorders suggesting that different mechanisms are responsible for various types of allergic disorders. For example, in atopic dermatitis (AD), one study reports that AD is associated with increased IL-4 Th2 cells (Kawamoto et al, 2006) whereas Machura et al (2006) report that children with AD have significantly lower IL-4 Th2 cells and TNF-α Th1 cells and therefore no distinct bias towards Th1 or Th2 profiles.…”