Table 1.

T_FH cell responses in humoral alloimmunity in transplantation

Model	location	TFH cell immune state and function	References
rat kidney transplant	GC TFH	proliferating Ki67+ GC TFH, increased IL-21+ TFH in splenic follicles and in serum from rats with ABMR (model using low dose cyclosporine)	[12]
mouse skin transplant	GC TFH	increased splenic ICOS+ PD-1+ TFH in skin rejection, which can be inhibited by anti-IL-21R Ab	[13]
human kidney transplant recipients	cTFH	increased IL-21+ and CFSElow donor-reactive blood TH (CD3+ CD8-) cells in patients with de novo DSA	[14]
mouse kidney transplant	GC TFH	increased CXCR5+ ICOS+ GC TFH from the draining lymph nodes of the transplanted kidney in mice with ABMR	[15]
mouse skin transplant	GC TFH	expansion of CXCR5+ PD-1hi GC TFH in response to a skin graft, which could be diminished by selective anti-CD28 treatment. The selective CD28 blockade inhibition of TFH-B cell interactions was CTLA-4-dependent and TFH-specific	[16]
human kidney transplant recipients	cTFH	increased of proliferating Ki67+ ICOS+ TFH, CCR7+CD127+ TFH and IL-21+ donor-specific TFH in DSA+ABMR+ versus DSA+ABMR-patients	[17]
human kidney transplant recipients	cTFH	ICOS+PD-1+CD38+CXCR5+ TFH detected in highly sensitized patients, which were decreased after desensitization by belatacept and proteasome inhibitor	[18]
mouse skin transplant	cTFH	ICOS+ PD-1+ TFH are enriched for donor-specific cells, ICOS+ PD-1 TFH expansion precedes DSA formation	[19]
human kidney transplant recipients	cTFH	decreased CXCR5+ICOS+PD-1+ TFH precedes de novo DSA formation	[20]
human kidney transplant recipients	cTFH	increased IL-21+ donor-specific T cells pre-transplant and post-tranplant predict allograft rejection	[21]
human kidney transplant recipients	cTFH	increased CD25+ CCR6+ TFH after in vitro restimulation correlates with DSA generation	[22]
mouse heart transplant	GC TFH	increased number of secondary follicles and TFH cells in spleen at day 50 post-transplant from mice showing heart ABMR	[23]
human kidney transplant recipients	cTFH	increased CD62L-CXCR3+ TFH and IL-21+ donor-specific TFH are associated with early DSA generation post-transplant	[24]
mouse heart	GC TFH	increased TFH numbers, GC size, high serum IL-21 in alemtuzumab-induced	[25]
transplant		chronic ABMR model, which could be reduced by anti-LFA-1 treatment
mouse skin transplant	GC TFH	expansion of CXCR5+ PD-1hi Bcl6+ donor-specific TFH that upregulated CTLA4 in response to a skin graft. Anti-CD28 treatment led to superior inhibition of donor-specific TFH and DSA formation compared to CTLA4-Ig.	[26]
human kidney transplant recipients	cTFH	CXCR5+ CCR7lo PD-1hi TFH correlated with de novo HLA sensitization post-transplant	[27]
human kidney transplant recipients	cTFH	increased CD40L+PD-1+ TFH in patients with de novo DSA at 1-year post-transplant	[28]
human kidney transplant recipients	cTFH	increased CXCR5+ CCR7+ TFH in ABMR patients with class II DSA compared to those with class I DSA	[29]
human kidney transplant recipients	cTFH	increased of both CXCR3-CCR6-TFH and CXCR3-CCR6+ TFH in patients with ABMR	[30]
non human primate kidney transplant	GC TFH	increased ICOS+PD-1hi GC TFH and size of GC in sensitized primates with ABMR after T cell–depleting induction	[31]
human kidney transplant recipients	cTFH	increased numbers of TFH cells in patients with pre-existent DSA	[32]
non human primate kidney transplant	GC TFH	Increased PD-1hi GC TFH and number of GCs in ABMR which could be decreased by anti-CD40 and belatacept treatment	[33]
mouse heart transplant	GC TFH	differentiation of transferred TCR-transgenic CD4 T cells (mimicking indirect pathway) into TFH phenotype that allow GC formation after heart transplantation of T cell-deficient mice	[34]