Analysis of robust innate immune response after transplantation in the absence of adaptive immunity.
BACKGROUND
Both animal models and clinical outcomes studies of transplantation suggest that antigen-independent mechanisms can alter graft survival and function. It has been suggested that antigen-independent processes interact with alloantigen-specific responses to augment the rejection reaction. A major link between antigen-specific adaptive immunity and pro-inflammatory stimuli is innate immunity. During transplantation, innate immunity may be stimulated by multiple factors, including ischemia, reperfusion, sterile injury, systemic stress, and cell death.


METHODS
We investigated the hypothesis that transplantation induces a potent innate immune response in a murine model of vascularized solid organ transplantation. In our studies, we analyzed three experimental groups: (a) alymphoid group in which both the donor and recipients strains lacked an adaptive immune response due to deletion of the recombinase activating gene, thus blocking production of both T cell and B cell antigen receptors; (b) syngeneic group in which the donors and recipients were genetically identical; and (c) allogeneic group in which the donors and recipients had a complete MHC mismatch. To analyze a large number of parameters we determined the level of expression of a panel of cytokines, chemokines, receptors, and cell surface markers by RNase protection assays. In addition, serum cytokines were determined by ELISA and the infiltration of inflammatory cells was assessed by histology.


RESULTS
Our results showed macrophage infiltration and up-regulation of multiple cytokines, chemokines, and chemokine receptors within the first day after transplantation in all groups, including the syngeneic and alymphoid recipients.


CONCLUSIONS
Our study demonstrated a robust innate immune response that is independent of adaptive immunity and natural killer cell responses.
He
Hongzhen
H
Laboratory of Molecular Immunology, Renal Division, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Stone
James R
JR
Perkins
David L
DL
D000818:Animals; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006650:Histocompatibility Testing; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D023421:Models, Animal; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology; D012260:Ribonucleases; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018925:Chemokines; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D012260:Ribonucleases