NDLI: Th1 cytokines, programmed cell death, and alloreactive T cell clone size in transplant tolerance

Content Provider	PubMed Central
Author	Kishimoto, Koji Sandner, Sigrid Imitola, Jaime Sho, Masayuki Li, Yongsheng Langmuir, Peter B. Rothstein, David M. Strom, Terry B. Turka, Laurence A. Sayegh, Mohamed H.
Copyright Year	2002
Abstract	The Th1 cytokines IL-2 and IFN-γ, which inhibit T cell proliferation and promote activation induced cell death, may be required to diminish alloreactive T cell numbers and to foster tolerance across full allogeneic barriers. However, we hypothesized that these cytokines might be dispensable when the alloreactive T cell clone size is relatively small, as is seen in recipients of minor-mismatched grafts. We show that alloreactive T cell clone size of C57BL/6 mice against multiple minor-mismatched 129X1/sv mice was ∼4–9-fold smaller than that against MHC-mismatched BALB/c mice. In the MHC-mismatched combination, CD28-B7 blockade by CTLA4Ig induced long-term graft survival in wild-type recipients, but this treatment was ineffective in IFNγ–/– or IL-2–/– recipients. In contrast, in the minor-mismatched combination, CTLA4Ig induced long-term allograft survival in wild-type, IFNγ–/– , and IL-2–/– recipients. Bcl-x L transgenic animals, which are defective in "passive" T cell death, are likewise sensitive to the effects of CTLA4Ig only in the setting of the minor-mismatch grafts. Therefore, the alloreactive T cell clone size is an important determinant affecting the need for Th1 cytokines and T cell death in tolerance induction. These data have implications for the design of tolerance strategies in transplant recipients with varying degrees of MHC mismatching.
Related Links	http://dx.doi.org/10.1172/JCI14947
Starting Page	1471
File Format	PDF
ISSN	15588238
e-ISSN	15588238
Journal	The Journal of Clinical Investigation
Issue Number	11
Volume Number	109
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2002-06-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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