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Table 1 Summary of specific effects of TNF inhibitors on T cells

From: Modulation of T-cell responses by anti-tumor necrosis factor treatments in rheumatoid arthritis: a review

  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] in nonresponders [27, 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]
Pneumococcal and influenza vaccine immunogenicity not reduced by anti-TNF [61, 62] Pneumococcal and influenza vaccine immunogenicity not reduced by anti-TNF [61, 62] Pneumococcal and influenza vaccine immunogenicity not reduced by anti-TNF [61, 62] Pneumococcal and influenza vaccine immunogenicity not reduced by anti-TNF [61, 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]
  1. Only references in which modifications of Th1/Th17 are correlated with clinical response are listed
  2. tm-TNF Jurkat is a model of Jurkat T cells transfected with a noncleavable form of TNF [23]
  3. Golimumab is not listed because too few data were available on this biologic
  4. – not available, Ab antibody, ADA adalimumab, ADCC antibody-dependent cell-mediated cytotoxicity, Ag antigen, CDC cell-dependent cytotoxicity, CMV cytomegalovirus, CZP certolizumab pegol, ETA etanercept, HBV hepatitis B virus, IFX infliximab, IL interleukin, iTreg inducible regulatory T cell, s soluble, SLO secondary lymphoid organs, Tb tuberculosis, Th T helper, tm transmembrane, TNF tumor necrosis factor, Tph T peripheral helper, Treg regulatory T cell, VZV varicella zoster virus