Islet allograft rejection can be mediated by CD4+, alloantigen experienced, direct pathway T cells of TH1 and TH2 cytokine phenotype.
BACKGROUND
It is widely believed that Thl cells that secrete interferon-gamma are primarily involved in the rejection of allografts whereas Th2 cells [interleukin(IL) 4 and IL-10] are thought to be protective of this process. However, the exact role and specificity of these helper T lymphocytes in mediating allograft damage is presently unknown.


METHODS
Th0, Th1, and Th2 cell lines specific for the class II MHC molecule H2IAb were adoptively transferred into T cell deficient, syngeneic, diabetic mice before transplantation of fully allogeneic C57BL/10 (H2b) or (CBKxBALB/c)F1 (H2k/d+Kb) islet grafts. T cells were 5-(and-6-)-carboxyfluorescein diacetate succinimidyl ester- (CFSE) labeled to allow detection, immunohistochemistry was performed, and IL-4 transcripts within the rejected islet grafts were quantified by reverse transcriptase polymerase chain reaction (RT-PCR).


RESULTS
Adoptive transfer (IV) of Th0-, Th1-, and Th2 IAb-specific T cells resulted in rejection of H2b islet allografts. CFSE-labeling demonstrated that these T cells were able to home to the graft site. CD4+ T cells and CD11b+ macrophages were present within the graft after adoptive transfer of both Thl and Th2 cells. Interestingly, CD8+ T cells and B cells were absent from these rejecting grafts. Even when Th2 cells were introduced directly at the graft site, prompt rejection was still observed despite the presence of increased IL-4 mRNA expression within the islet allografts.


CONCLUSIONS
Th2 and Th0 alloreactive CD4+ T helper cells can reject islet grafts with similar efficiency to Th1 cells. These results suggest that deviation of the immune response from a Th1 to Th2 phenotype will not be sufficient to allow successful engraftment of allogeneic organs or tissues.
Barbara
J A
JA
Nuffield Department of Surgery, University of Oxford, The John Radcliffe Hospital, Headington, UK.
Turvey
S E
SE
Kingsley
C I
CI
Spriewald
B M
BM
Hara
M
M
Witzke
O
O
Morris
P J
PJ
Wood
K J
KJ
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016207:Cytokines / Q000235:genetics*; D006084:Graft Rejection / Q000473:pathology; D015847:Interleukin-4 / Q000096:biosynthesis; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007519:Isoantigens / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism* / Q000502:physiology; D018418:Th2 Cells / Q000378:metabolism* / Q000502:physiology; D014184:Transplantation, Homologous
D015704:CD4 Antigens; D016207:Cytokines; D007519:Isoantigens; D015847:Interleukin-4