1: Kidney Int. 2002 Aug;62(2):627-31. 

Regulatory functions of alloreactive Th2 clones in human renal transplant
recipients.

Kist-van Holthe JE, Gasser M, Womer K, Najafian N, Dong V, Samsonov DV, Geehan
CS, Chandraker A, Sayegh MH, Waaga AM.

Division of Nephrology, Children's Hospital, and Renal Division, Laboratory of
Immunogenetics and Transplantation, Brigham and Women's Hospital, Harvard
Medical School, Boston, Massachusetts 02115, USA.

BACKGROUND: Chronic allograft rejection is the major clinical problem in organ
transplantation. There is evidence that indirect T cell recognition of
donor-specific HLA peptides may play an important role in the immunopathogenesis
of chronic allograft rejection. We have recently shown that HLA
allopeptide-specific T cell clones generated from renal transplant recipients
with chronic allograft nephropathy are of the Th1 phenotype, while those from
stable patients are Th2. There is evidence in experimental animal models of
autoimmunity and transplantation that Th2 cells may function to regulate immune
responses, but the biological relevance of these observations in humans has not
been reported. METHODS: The purpose of this study was to investigate the
putative regulatory functions of alloreactive human Th2 clones. HLA-DR
allopeptide-specific Th1 and Th2 cell clones were generated from peripheral
blood lymphocytes of human renal allograft recipients with chronic allograft
nephropathy (CAN) or with stable renal function (SRF), respectively. RESULTS: An
in vitro co-culture system showed that the proliferative responses of Th1 clones
from patients with CAN were significantly inhibited by the Th2 clones in
response to the donor-derived HLA allopeptides. In addition, co-culture of the
Th2 clones inhibited cytokine production (IFN-gamma) by the Th1 clones in
response to the donor-specific peptides. The regulatory functions of Th2 clones
were antigen-specific since they only occurred when both the Th1 and Th2 clones
were reactive to the same HLA-DR allopeptide, and were mediated by IL-4 and
IL-10. CONCLUSIONS: This is the first demonstration, to our knowledge,
indicating that Th2 cells may function to regulate indirect Th1 alloimmune
responses that are critical for the progression of CAN in humans.

PMID: 12110027 [PubMed - indexed for MEDLINE]


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