Vascularized lymph node transplantation induces graft-versus-host disease in chimeric hosts

The role of lymph nodes (LNs) in adaptive immune responses has been the subject of extensive research. In previous studies, the surgical removal of lymph nodes from rat hind limbs prevented the development of lethal graft-versus-host disease (GVHD) after allogeneic hind limb transplantation to chimeric recipient rats. The purpose of this study was to establish the role of the cellular fraction versus the microenvironment of LNs in the development of GVHD in this model.

A rat model for vascularized LN transplantation was developed and graft-versus-host responses were compared after: 1) naive ACI LN cells were infused into Wistar-Furth (WF) rats as chimeric recipients (e.g. [ACI-->WF]); 2) vascularized WF lymph nodes were transplanted to syngeneic WF recipients; 3) nonvascularized ACI lymph nodes were transplanted to [ACI-->WF] chimeric recipients; 4) vascularized ACI lymph nodes were transplanted to [ACI-->WF] chimeric recipients.

Transplantation of vascularized ACI lymph nodes to [ACI-->WF] chimeric recipient rats resulted in severe and sometimes lethal GVHD. In contrast, neither the infusion of purified ACI LN cells nor the transplantation of nonvascularized LNs led to GVHD in chimeric recipients.

When introducing allogeneic cells into chimeric recipients, concomitant transplantation of the vascularized LN microenvironment makes a manifest difference between induction and absence of GVHD. This illustrates the important role of the LN microenvironment in adaptive immune responses.