The impact of immune-activating processes following transplantation on chronic allograft nephropathy.
BACKGROUND
The long-term success of organ transplantation is influenced by numerous alloantigen-dependent and -independent risk factors. However, only very little information is presently available on the influence of systemic immune-activating processes following organ engraftment.


METHODS
To simulate the clinical situation of sequential organ transplantation, rat renal allograft recipients received additional immune activating stimuli (secondary donor-specific and third-party skin grafts) after transplantation at serial time intervals (4 and 8 weeks). The overall observation period was 16 weeks.


RESULTS
All control animals survived the observation period. In contrast, recipients receiving additional third-party or donor-specific skin grafts were beginning to die 12 weeks after organ engraftment with only few animals surviving 16 weeks. Systemic immune activation by additional third-party and in particular by additional donor-specific skin grafts resulted in significant temporary and long-term functional deterioration. Morphologic changes progressed significantly, particularly after a secondary challenge with donor-specific skin grafts. ED1+ monocytes/macrophages, T-cell infiltrates, and intragraft mRNA expression for CD25 were significantly elevated by 16 weeks, following an additional immune challenge. Analysis of early intragraft events showed strong up-regulation of CD25 transcripts, suggesting fast stimulation of intragraft immune processes.


CONCLUSIONS
Both alloantigen-specific and -unspecific systemic immune activation processes, following experimental organ transplantation, contribute to chronic graft deterioration. Those results seem relevant for long-term immunosuppressive protocols and clinical situations of sequential organ transplantation.
Heidenhain
Christoph
C
Department of General and Transplantation Surgery Charité-Campus Virchow Clinic, Berlin, Germany.
Reutzel-Selke
Anja
A
Bachmann
Ulrike
U
Jonas
Sven
S
Pascher
Andreas
A
Ulrich
Frank
F
Pratschke
Johann
J
Neuhaus
Peter
P
Volk
Hans-Dieter
HD
Tullius
Stefan G
SG
D000818:Animals; D002908:Chronic Disease; D015870:Gene Expression; D006085:Graft Survival; D007107:Immune System / Q000503:physiopathology; D007158:Immunologic Techniques; D007519:Isoantigens / Q000276:immunology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D007519:Isoantigens; D015375:Receptors, Interleukin-2