Human allograft acceptance is associated with immune regulation
A.M. VanBuskirk, … , R.P. Pelletier, C.G. Orosz
A.M. VanBuskirk, … , R.P. Pelletier, C.G. Orosz
Published January 1, 2000
Citation Information: J Clin Invest. 2000;106(1):145-155. https://doi.org/10.1172/JCI9171.
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Article

Human allograft acceptance is associated with immune regulation

Abstract

The ultimate goal of transplantation is drug-free allograft acceptance, which is rarely encountered in transplant recipients. Using a novel human-to-mouse “trans vivo” delayed-type hypersensitivity assay, we assessed donor-reactive cell-mediated immune responses in kidney and liver transplant patients, four of whom discontinued all immunosuppression. One of these subjects (J.B.) rejected his graft after 7 years of stable function, while the others (D.S., R.D., M.L.) continue to have excellent graft function 5, 28, and 4 years after the cessation of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor and recall antigens whereas PBMCs from patients D.S., R.D., and M.L. responded strongly to recall, but not donor, antigens. Furthermore, when donor and recall antigens were colocalized, the recall response in these three patients was inhibited. This donor antigen–linked nonresponsiveness was observed in four other patients who are still maintained on immunosuppression. The weakness of donor-reactive DTH responses in these patients is due to donor alloantigen-triggered regulation that relies on either TGF-β or IL-10. In D.S., regulation is triggered by a single donor HLA Class I antigen, either in membrane-bound or soluble form. This demonstrates that allograft acceptance in humans is associated with an immune regulation pattern, which may be useful in the diagnosis and/or monitoring of transplant patients for allograft acceptance.

Authors

A.M. VanBuskirk, W.J. Burlingham, E. Jankowska-Gan, T. Chin, S. Kusaka, F. Geissler, R.P. Pelletier, C.G. Orosz

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Figure 1

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Trans vivo DTH responses: donor antigen–linked DTH nonresponsiveness to ...
Trans vivo DTH responses: donor antigen–linked DTH nonresponsiveness to TT. (a) Eight million PBMCs from patient D.S. were injected into the footpads of SCID mice and the swelling measured after 24 hours. This background swelling was used to calculate the specific swelling when PBMCs plus the different antigens were included in the injection mixture. Injection of PBMCs plus self antigens (Ag) did not result in swelling, whereas injection of PBMCs plus self Ag plus TT resulted in swelling (not shown). These data are combined from six separate experiments performed over 8 months. (b) Eight million PBMCs from patient J.B. were injected into the footpads of SCID mice and the swelling measured after 24 hours. This background swelling was used to calculate the specific swelling when PBMCs plus donor alloantigens, TT, or donor alloantigens plus TT were included in the injection mixture. Data are combined from three separate experiments over 9 months.