Background
Role of T cells in RA
Role of TNF in the development of the immune system
Role of TNF in T-cell differentiation, activation, and maturation: action of TNF inhibitors
Effects of anti-TNF on T-helper cell subset differentiation
Anti-TNF treatments affect Tregs in RA
Consequences of anti-TNF treatments on T-cell control of infections
Consequences of anti-TNF on T-dependent B-cell responses
Conclusion
IFX | ADA | CZP | ETA | |
---|---|---|---|---|
SLO | – | – | – | Patients lack germinal center development in tonsils [13] |
Th1 |
in nonresponders [27] |
in responders [26] | – |
in responders [26] |
Th17 |
in nonresponders [27] |
in nonresponders [32] | – | |
– |
Associated with ultrasound improvement [30] | – |
Associated with ultrasound improvement [30] | |
– | Good response correlated with low levels of Th17 [34] | - | No correlation of good response with low levels of Th17 [34] | |
Induction of IL-17+ IL-10+ CD4+ T cells [35] | Induction of IL-17+ IL-10+ CD4+ T cells [35] | Induction of IL-17+ IL-10+ CD4+ T-cells [35] | Induction of IL-17+ IL-10+ CD4+ T cells [35] | |
Tph | Decrease in Tph [39] | – | Decrease in Tph [39] | Decrease in Tph [39] |
Treg | Restoration of functional Tregs [44] | Expansion of iTregs through tmTNF-Mo/TNF-RII T-cell interaction [45] | – | No expansion of iTregs [45] |
T-cell activation | Induction of STAT4 and STAT6 [36] | – | – | – |
Reverse signaling | Induction of IL-10 in tm-Jurkat cells [23] | – | – | No induction of IL-10 in tm-Jurkat cells [23] |
Suppression of tm-Jurkat cell proliferation [23] | – | – | No suppression of tm-Jurkat cell proliferation [23] | |
JNK activation in tm-Jurkat [23] | – | – | No JNK activation in tm-Jurkat [23] | |
Metabolism | Not affected [21] | – | – | – |
Infections | Tb reactivation [48] | Tb reactivation [48] | Tb reactivation [48] | Lower rate of Tb reactivation than with Abs [48] |
Reduction of Tb-specific CD8+ memory cells [49] | – | – | – | |
Inhibition of CD4+ response [50] | Inhibition of CD4+ response [50] | – | Inhibition of CD4+ response less pronounced than with Abs [50] | |
Risk of listeria infection [51] | – | – | Lower risk of listeria infection than with sIFX [51] | |
CD4+ response to CMV Ags conserved [54] | CD4+ response to CMV Ags conserved [54] | – | CD4+ response to CMV Ags conserved [54] | |
Reactivation of HBV chronic infection [55] | Reactivation of HBV chronic infection [55] | – | Possibly less reactivation of HBV chronic infection [55] | |
Vaccination | Inadvertent vaccination with live vaccines (yellow fever, VZV) suggest they may be safer than expected [62] | Inadvertent vaccination with live vaccines (yellow fever, VZV) suggest they may be safer than expected [62] | Inadvertent vaccination with live vaccines (yellow fever, VZV) suggest they may be safer than expected [62] | Inadvertent vaccination with live vaccines (yellow fever, VZV) suggest they may be safer than expected [62] |
No specific effect of TNF inhibitors on HBV protective immunity [56] | No specific effect of TNF inhibitors on HBV protective immunity [56] | – | No specific effect of TNF inhibitors on HBV protective immunity [56] | |
Antidrug antibodies | A proportion of patients develop antidrug antibodies | A proportion of patients develop antidrug antibodies | A proportion of patients develop antidrug antibodies | Fewer patients develop antidrug antibodies which appear to be less neutralizing |
Cell death | Induction of ADCC and CDC in tm-Jurkat [24] | Induction of ADCC and CDC in tm-Jurkat [24] | No induction of ADCC and CDC in tm-Jurkat [24] | Lower induction of ADCC or CDC in tm-Jurkat in tm-Jurkat [24] |
Loss of cell viability of tm-Jurkat [24] | Loss of cell viability of tm-Jurkat [24] | No loss of cell viability of tm-Jurkat [24] | No loss of cell viability of tm-Jurkat [24] | |
Apoptosis | Apoptosis of tm-Jurkat [24] | Apoptosis of tm-Jurkat [24] | No apoptosis of tm-Jurkat [24] | No apoptosis of tm-Jurkat [24] |
Apoptosis of CD3-activated T cells [66] | Apoptosis of CD3-activated T cells [66] | No apoptosis of CD3-activated T cells [66] | Apoptosis of CD3-activated T cells [66] | |
Spontaneous in-vitro apoptosis of CD4+CD25+ T cells diminished [25] | – | – | – |