Francois Cedric G, Brouha Pascal C R, Laurentin-Perez Luis A, Perez-Abadia Gustavo, Grossi Federico V, Barker John H, Hewitt Charles W, Kon Moshe, Ramsamooj Rajendra, Maldonado Claudio
Plastic Surgery Research, Department of Surgery, University of Louisville, KY, USA.
Transplantation. 2006 May 27;81(10):1435-41. doi: 10.1097/01.tp.0000209210.75211.57.
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.
淋巴结（LNs）在适应性免疫反应中的作用一直是广泛研究的主题。在先前的研究中，从大鼠后肢手术切除淋巴结可预防同种异体后肢移植到嵌合受体大鼠后致死性移植物抗宿主病（GVHD）的发生。本研究的目的是确定在该模型中，淋巴结的细胞成分与微环境在GVHD发生中的作用。
建立了一个血管化淋巴结移植的大鼠模型，并在以下情况下比较移植物抗宿主反应：1）将未致敏的ACI淋巴结细胞注入作为嵌合受体的Wistar-Furth（WF）大鼠（例如[ACI→WF]）；2）将血管化的WF淋巴结移植到同基因的WF受体；3）将非血管化的ACI淋巴结移植到[ACI→WF]嵌合受体；4）将血管化的ACI淋巴结移植到[ACI→WF]嵌合受体。
将血管化的ACI淋巴结移植到[ACI→WF]嵌合受体大鼠中导致严重的、有时是致死性的GVHD。相比之下，无论是注入纯化的ACI淋巴结细胞还是移植非血管化的淋巴结，都不会导致嵌合受体发生GVHD。
在将同种异体细胞引入嵌合受体时，血管化淋巴结微环境的伴随移植在诱导GVHD和不发生GVHD之间产生了明显差异。这说明了淋巴结微环境在适应性免疫反应中的重要作用。
