Different patterns in donor-specific production of T-helper 1 and 2 cytokines by cells infiltrating the rejecting cardiac allograft.
BACKGROUND
Cytokines play an important role in allograft rejection. The local production of cytokines by T-helper 2 cells within an allograft could influence the induction of graft rejection.


METHODS
Therefore we studied the in vitro production of cytokines by cells infiltrating the graft. graft-infiltrating cell cultures derived from human endomyocardial biopsy specimens more often produced interleukin-2 (p < 0.001), interferon-gamma (p < 0.001), interleukin-4 (p = 0.02), and interleukin-6 (p = 0.04) after stimulation with a B-cell line obtained from the heart donor than after stimulation with a third-party B-cell line. Furthermore, the levels of these cytokines were significantly higher after donor stimulation than after third-party stimulation (p < 0.001).


RESULTS
Within the first 90 days after heart transplantation, significantly higher levels of interleukin-2 (p = 0.050 and interferon-gamma (p = 0.02) were produced by donor-stimulated lymphocyte cultures derived from biopsy specimens taken during a rejection episode compared with cultures from biopsy specimens taken during a period without rejection. After 90 days, the levels of T-helper 1 cytokine (interleukin-2 and interferon-gamma) production were, irrespective of the rejection grade, comparable with those found in the cultures from rejection biopsy specimens taken early after transplantation. With regard to T-helper 2 cytokines (interleukin-4 and interleukin-6), no relation was found with the presence of rejection at any time after transplantation.


CONCLUSIONS
These data suggest that in the first 3 months after heart transplantation, acute rejection is associated with the production of increased levels of T-helper 1 cytokines but not of T-helper 1 cytokines but not of T-helper 2 cytokines by donor stimulated graft-infiltrating lymphocytes. Thereafter, the T-helper 1 cytokine production of graft-infiltrating lymphocytes remained high, suggesting a continuous state of immunologic activity even in the absence of rejection.
van Besouw
N M
NM
Department of Internal Medicine, Erasmus University Rotterdam, The Netherlands.
Daane
C R
CR
Vaessen
L M
LM
Balk
A H
AH
Claas
F H
FH
Zondervan
P E
PE
Jutte
N H
NH
Weimar
W
W
D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004699:Endocardium / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009206:Myocardium / Q000473:pathology; D018417:Th1 Cells / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism* / Q000473:pathology; D014019:Tissue Donors
D016207:Cytokines; D007378:Interleukins; D007371:Interferon-gamma