Functional human regulatory T cells fail to control autoimmune inflammation due to PKB/c-akt hyperactivation in effector cells

Enhanced Activity of Akt in Teff Cells From Children With Lupus Nephritis Is Associated With Reduced Induction of Tumor Necrosis Factor Receptor–Associated Factor 6 and Increased OX40 Expression

“…Intriguingly, several recent studies have demonstrated that Teff cells are resistant to Treg cell-mediated suppression in murine models of SLE and in humans (13,15,17,18). Moreover, in patients with juvenile idiopathic arthritis, hyperactivation of the Akt pathway in Teff cells from the site of inflammation causes these cells to become resistant to suppression (18).…”

“…Moreover, in patients with juvenile idiopathic arthritis, hyperactivation of the Akt pathway in Teff cells from the site of inflammation causes these cells to become resistant to suppression (18). The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated (phosphorylated) downstream of many receptors on the T cell surface, including the T cell receptor and CD28, cytokine, adhesion, and chemokine receptors (19)(20)(21), and this pathway promotes various cell responses associated with survival, cell division, and proliferation (22,23).…”

“…Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (35,36). Eight patients had active lupus nephritis (median SLEDAI-2K score 14 [range [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]; median renal SLEDAI-2K score 12 [range [8][9][10][11][12]), and 9 had inactive lupus nephritis (median SLEDAI-2K score 0 [range 0-2]; median renal SLEDAI-2K score 0). At the time of sampling, patients with lupus nephritis were receiving no treatment (n ϭ 3), mycophenolate mofetil (MMF) plus prednisone (n ϭ 6), prednisone alone (n ϭ 2), MMF plus prednisone plus hydroxychloroquine (n ϭ 2), prednisone plus hydroxychloroquine (n ϭ 1), MMF plus cyclosporine (n ϭ 2), or MMF alone (n ϭ 1).…”

Comparison of Blood and Synovial Fluid Th17 and Novel Peptidase Inhibitor 16 Treg Cell Subsets in Juvenile Idiopathic Arthritis

“…Treg, like Th17 cells, are found in high numbers with in the inflamed synovium of RA [45] and JIA [46][47][48] Table Table 1 Subtype hi PI16+ Treg cells to CCR4 ligand CCL17, CCR6 ligand CCL20 and both CCL17 and CCL20 from healthy children PBMC (n=5) compared with PBMC (n=10) and SFMC (n=6) of JIA patients. Cells were analysed by flow cytometry, gated on the CD4+ CD25 hi CD127 low PI16+ Treg cell population.…”

Recognition of self-heat shock protein 60 by T cells from patients with atopic dermatitis

“…Interestingly, a recent study by Wehrens et al revealed that highly activated T effector cells are resistant to suppression through PKB/c-akt hyperactivation. This might also be an explanation why these phenotypically regulatory cells fail to suppress T effector cells in vitro and needs further investigation (Wehrens et al 2011). In atopic diseases, it has been speculated whether specific targeting of T cells could provide a novel immunomodulatory pathway for treatment.…”