Detection of single cells secreting IFN-gamma, IL-6, and IL-10 in irreversibly rejected human kidney allografts, and their modulation by IL-2 and IL-4.
The frequency of isolated low-density graft-infiltrating cells (GIC) secreting IFN-gamma, IL-6, and IL-10 was studied in 8 cases of irreversible rejection of human renal allografts, using ELISA and SPOT-forming cells (ELISPOT) assays. The GIC were mostly CD8+ T cells, although CD4+ T cells, B cells, and macrophages could also be detected. On the average, in 10(6) cells, 189 secreted IFN-gamma, 747 IL-10, and 17114 IL-6. Culture of GIC in the presence of IL-2 resulted in an increase in the frequency of IFN-gamma-producing cells (IFN-gamma-PC), in a dose-dependent manner, with an optimal 6.5-fold increase at 50 U/ml. In contrast, 25 U/ml IL-4 decreased the frequency of spontaneous and IL-2-induced IFN-gamma-PC by 71.3% and 52.8%, respectively. Furthermore, IL-4 reduced the frequency of IL-6-PC (56.8%). By this new approach to graft rejection, it becomes easier to determine cytokine profiles within an allograft and to study their modulation by different agents. It could be a useful model of study for the development of new treatment.
Merville
P
P
Schering-Plough Laboratory for Immunological Research, Hôpital Edouard Herriot, Lyon, France.
Pouteil-Noble
C
C
Wijdenes
J
J
Potaux
L
L
Touraine
J L
JL
Banchereau
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology*; D007694:Killer Cells, Natural; D009000:Monocytes / Q000502:physiology; D010641:Phenotype; D014184:Transplantation, Homologous / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma