Table 1.
Diseases in which Tcon cells resist Treg-mediated suppression.
| Disease | Subject | Type of effector cell | Suggested mechanism | Study |
|---|---|---|---|---|
| Juvenile idiopathic arthritis (JIA) | Human | Synovial fluid CD4+ CD25− | Enhanced activation | Haufe et al. (23) |
| Synovial fluid CD4+ and CD8+ Teffa | Akt hyperactivation in response to IL-6/TNFα | Wehrens et al. (24, 25) | ||
| Rheumatoid arthritis (RA) | Human | Peripheral blood CD4+CD25− | Increased TRAIL expression on Teff leading to Treg apoptosis | Xiao et al. (26) |
| Type 1 diabetes (T1D) | NOD mice | Splenic CD4+CD25− | ND | You et al. (15) |
| DO11.10 RIP-mOVA mice | Lymph node CD4+CD25− | Increased IL-21 | Clough et al. (18) | |
| NOD mice | Splenic CD4+CD25− | ND | D’Alise et al. (20) | |
| NOD mice | Splenic CD4+ and CD8+ Teff | Reduced ganglioside M1 expression on Teff | Wu et al. (21) | |
| Human | Peripheral blood CD4+CD25− | ND | Schneider et al. (27) | |
| Peripheral blood CD4+CD25− | ND | Lawson et al. (28) | ||
| Systemic lupus erythematosus (SLE) | MRL/lpr and NZB/WF1 mice | Splenic and lymph node CD4+CD25− | ND | Monk et al. (14) |
| MRL/lpr mice | Lymph node CD4+CD25− | ND | Parietti et al. (19) | |
| Human | Peripheral blood CD4+CD25− | ND | Venigalla et al. (29) | |
| Peripheral blood CD4+CD25− | ND | Vargas-Rojas et al. (30) | ||
| Peripheral blood CD4+CD45RA−FoxP3− | Akt hyperactivation, upregulation of OX40 and impaired TRAF6 in Teff | Kshirsagar et al. (116) | ||
| Experimental autoimmune encephalitis (EAE) | FoxP3.gfp KI mice | CNS CD4+GFP− | High IL-6 and TNFα | Korn et al. (16) |
| C57BL/6 mice | CNS CD4+CD25− | ND | O’Connor et al. (17) | |
| B6.SLE mice | Splenic CD4+CD25− | ND | Wilhelm et al. (22) | |
| Multiple sclerosis (MS) | Human | Peripheral blood CD3+ Teffb | Accelerated production of IL-6 and higher expression of IL-6R on Teff leads to Akt hyperactivation | Trinschek et al. (31) |
| Peripheral blood CD4+CD25− | Increased IL-6 induction of pSTAT3 | Schneider et al. (32) | ||
| Peripheral blood CD4+CD25− | Increased Granzyme B production by Teff w/TCR activation/IL-6 stimulation, inactivating Tregs | Bhela et al. (33) | ||
| Inflammatory bowel disease (IBD) | Human | Lamina propria CD4+CD25− | Higher expression of Smad7 interfering with TGF-β signaling | Fantini et al. (35) |
| Lamina propria CD4+CD25− | Increased IL-15 in lamina propria | Hmida et al. (34) |
ND, not determined; CNS, central nervous system.
aTeff – total synovial fluid or peripheral blood mononuclear cells (as indicated) isolated as CD4+ or CD8+.
bTeff – contains both CD4+ and CD8+ Teff cells, isolated as CD3+.