Figure 1.

Lymphostromal crosstalk in thymic grafts. (A) Developing thymocytes communicate with antigen (Ag)-presenting cells (APC) through HLA-TCR interactions. APCs include both thymic stromal cells and hematopoietic cells. In thymic grafts these APCs can be host-derived (in blue) or donor-derived (in orange). The thymus tissue donor and the athymic patient are not HLA-matched. (B) After thymus transplantation, lymphoid progenitors migrate from the recipient’s bone marrow into the HLA-mismatched thymic graft. In the thymic cortex developing thymocytes undergo positive selection of competent T-cells through low-affinity engagement of their TCR with HLA-bound antigens. In the case of serendipitous, partial HLA-matching between donor and recipient, traditional antigen-presentation by cTECs may occur (1). Donor-derived fibroblasts (Fb) possibly also contribute to this (2). In theory, host-derived APCs of hematopoietic origin in the graft may also contribute to positive selection, for example through direct thymocyte-thymocyte interactions (3). Positively selected DP thymocytes then undergo negative selection to eliminate autoreactive T-cells. In the thymic graft this may also start in the cortex thanks to direct HLA-TCR mediated interactions with DCs of host origin (4). In normal thymus tissue generation of self-tolerance predominantly takes place in the medulla. If there is partial HLA-matching between the donor and the recipient, donor-derived mTECs and possibly fibroblasts can contribute to this in thymic grafts (5 and 6). Host-derived hematopoietic cells, in particular DCs, may also play a role (7). Additionally, it is possible that upon transplantation chimeric thymic stroma develops with stromal cells of host origin, both in the cortex and the medulla (8). Figure created with BioRender.com.