In vivo modulation of the allogeneic immune response by human fetal kidneys: the role of cytokines, chemokines, and cytolytic effector molecules.
BACKGROUND
We have recently demonstrated that human fetal renal tissue, implanted under the kidney capsule of severe immunodeficient rats, escapes early destruction by intraperitoneal infusion of allogeneic human peripheral blood mononuclear cells, compared with the rapid rejection of implants of human adult kidney tissue. Variable amounts of human mononuclear infiltrates were seen in the transplanted fetal kidney, however, prolonged survival of the fetal tissue (maintenance of graft architecture and significant growth) was independent of the cellular infiltrate.


METHODS
We have used this experimental model to sequentially analyze transcript levels of interferon-gamma and interleukin (IL)-2 (T helper 1 cytokines), IL-4 and IL-10 (T helper 2 cytokines), RANTES, MIP1beta (beta chemokines) and their receptor CCR5, and Fas ligand (cytolytic effector molecule). Analysis was performed by reverse transcriptase-polymerase chain reaction, in both fetal and adult kidney grafts, after infusion of allogeneic human peripheral blood mononuclear cells.


RESULTS
Transcript levels of interferon-gamma and IL-2 in the fetal grafts were markedly reduced throughout follow-up, compared with those observed in the adult implants. Peak levels of these cytokines appeared late in the rejection process. Concomitant with these findings, IL-4 mRNA was up-regulated during the early phase, whereas IL-10 mRNA persisted throughout the rejection process, indicating that a T helper 2 bias occurred in the fetal grafts. In addition, RANTES (after an early peak), MIP1beta, CCR5, and Fas ligand mRNA levels were suppressed in the fetal grafts compared with those in the adult grafts.


CONCLUSIONS
These findings indicate that the immune response of kidney rejection is dependent on whether the target organ is of fetal or adult origin, and suggest that an allogeneic immune system mounts a T helper 2-biased response when the target organ is of fetal origin.
Dekel
B
B
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Marcus
H
H
Herzel
B H
BH
Böcher
W O
WO
Passwell
J H
JH
Reisner
Y
Y
D000328:Adult; D000818:Animals; D000917:Antibody Formation; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D053222:Fas Ligand Protein; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000196:embryology*; D016030:Kidney Transplantation; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D009000:Monocytes / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D019713:Receptors, CCR5 / Q000235:genetics; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019713:Receptors, CCR5