Table 1.
Tertiary lymphoid organs associated with allograft rejection or acceptance
| Promoting Rejection | ||||
|---|---|---|---|---|
| Organ | Species | Supporting evidence | TLO characteristics | Reference |
| Heart | Human | Peripheral nodal addressin is expressed in acutely rejected allografts | PNAd | 22 |
| Human | TLOs containing memory B cells and plasma cells are in proximity to allograft vasculopathy lesions | PNAd, memory B cells, T cells, LT-β, CCL19, CCL21 | 25 | |
| Human | TLOs are present in hearts undergoing chronic rejection | T and B cells, Ki67+ cells, FDC | 23 | |
| Mouse | Presence of TLOs composed of T- and B-cell zones correlates with acute or chronic allograft rejection | T and B cells, PNAd+ HEV | 26 | |
| Kidney | Human | TLOs with evidence of local humoral immune response are present in chronically rejected human allografts | PNAd, podoplanin, B cells (GC),T cells, FDC, CCL21, CXCL13, LTβR | 24 |
| Human | TLOs are present in kidneys undergoing chronic rejection | T cells, B cells, Ki67+ cells, FDC | 23 | |
| Human | Peripheral nodal addressin is expressed in allografts undergoing acute rejection | PNAd | 21 | |
| Lung | Human | TLOs are associated with obliterative bronchiolitis lesions | PNAd+ HEV, memory effector T cells | 27 |
| Rat | TLOs serve as sites of local immune response that accelerate onset of lung rejection | Lymphocyte infiltration into preexisting TLOs | 29 | |
| Trachea | Mouse | TLOs form in lungs after intrapulmonary transplantation of tracheal allografts Rejection of intrapulmonary tracheal allografts is independent of recipient secondary lymphoid organs |
T and B cells, Ki67+ cells PNAd+ HEV |
28 |
| Aorta | Rat | TLOs containing germinal center B cells which produce donor-specific alloantibodies and promote rejection | T cells, B cells (GC), HEV | 23 |
| Skin | Mouse | Donor skin graft bearing TLOs cause robust humoral rejection in an allogeneic host | PNAd+ HEV | 10 |
| Skin, Vascularized composite grafts | Human, Nonhuman Primate, Rat | Expression level of peripheral nodal addressin correlates with rejection | T and B cells, PNAd+ HEV | 30 |
| Promoting Acceptance | ||||
| Lung | Human | TLOs are associated with clinically insignificant acute rejection and are not associated with the development of chronic rejection | T (mainly CD4+) and B cells | 31 |
| Human | Rejection is associated with decrease in TLOs | Plasma cells | 32 | |
| Mouse | TLOs rich in Foxp3+ regulatory T cells are present in long term accepted grafts | Foxp3+ T cells, B cells, DCs, PNAd+ HEV, CCL21 | 33 | |
| Kidney | Mouse | TLOs form in allografts that are spontaneously accepted | Foxp3+ T cells, T and B cells, DCs, macrophages, podoplanin, PNAd+ HEV | 34 |
| Mouse | Nodular infiltrates rich in Foxp3+ regulatory T cells are present in spontaneously accepting allografts | Foxp3+ T cells, T (mainly CD4+) and B cells, DC | 35 | |
(TLO: tertiary lymphoid organ; PNAd: peripheral nodal addressin; HEV: high endothelial venules; FDC: follicular dendritic cells; DC: dendritic cells; GC: germinal center)