TY - JOUR
T1 - Prolongation of allograft survival by Nippostrongylus brasiliensis is associated with decreased allospecific cytotoxic T lymphocyte activity and development of T cytotoxic cell type 2 cells
AU - Liwski, Robert
AU - Zhou, Juan
AU - McAlister, Vivian
AU - Lee, Timothy D.G.
PY - 2000/5/15
Y1 - 2000/5/15
N2 - Background. We have demonstrated that infection with Nippostrongylus brasiliensis (Nb), which induces strong type 2 responses, prolongs kidney allograft survival in rats. Here, we confirm that this effect is not species- specific and address immune modulation in allospecific T-cell responses mediated by nematode infection. Methods. C57BL/6 mice were injected with Nb or phosphate-buffered saline. Four days later, mice were transplanted with BALB/c hearts and graft survival was assessed. In other experiments, Nb- infected mice were immunized with BALB/c spleen cells and allospecific T-cell responses were determined in vitro. Results. In this study, we show that Nb prolongs cardiac allograft survival in mice. Further, spleen T-cells from Nb- infected, allo-immunized mice exhibit reduced allospecific cytotoxic T- lymphocyte activity. In contrast, allospecific proliferation of T cells in the mixed lymphocyte reaction was not reduced by Nb, ruling out immunosuppression as the mechanism of Nb-induced allograft survival. Nb infection induced IL-4 and IL-6 and inhibited IFN-γ production by T cells in response to allo-antigen. Furthermore, anti-IL-4 treatment reduced allospecific T-cell proliferation from Nb-infected but not control mice, indicating the that type 2 allospecific T cells develop in the presence of Nb. We also double-stained T cells for CD8 and IL-4 and showed that Nb induces an 8-fold increase in Tc2 cell numbers. Conclusions. These results are consistent with a hypothesis that Nb mediates prolongation of allograft survival through induction of type 2 immunity, including the development of regulatory Tc2 cells, and subsequent inhibition of allospecific cytotoxic T- lymphocyte activity.
AB - Background. We have demonstrated that infection with Nippostrongylus brasiliensis (Nb), which induces strong type 2 responses, prolongs kidney allograft survival in rats. Here, we confirm that this effect is not species- specific and address immune modulation in allospecific T-cell responses mediated by nematode infection. Methods. C57BL/6 mice were injected with Nb or phosphate-buffered saline. Four days later, mice were transplanted with BALB/c hearts and graft survival was assessed. In other experiments, Nb- infected mice were immunized with BALB/c spleen cells and allospecific T-cell responses were determined in vitro. Results. In this study, we show that Nb prolongs cardiac allograft survival in mice. Further, spleen T-cells from Nb- infected, allo-immunized mice exhibit reduced allospecific cytotoxic T- lymphocyte activity. In contrast, allospecific proliferation of T cells in the mixed lymphocyte reaction was not reduced by Nb, ruling out immunosuppression as the mechanism of Nb-induced allograft survival. Nb infection induced IL-4 and IL-6 and inhibited IFN-γ production by T cells in response to allo-antigen. Furthermore, anti-IL-4 treatment reduced allospecific T-cell proliferation from Nb-infected but not control mice, indicating the that type 2 allospecific T cells develop in the presence of Nb. We also double-stained T cells for CD8 and IL-4 and showed that Nb induces an 8-fold increase in Tc2 cell numbers. Conclusions. These results are consistent with a hypothesis that Nb mediates prolongation of allograft survival through induction of type 2 immunity, including the development of regulatory Tc2 cells, and subsequent inhibition of allospecific cytotoxic T- lymphocyte activity.
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U2 - 10.1097/00007890-200005150-00029
DO - 10.1097/00007890-200005150-00029
M3 - Article
C2 - 10830231
AN - SCOPUS:0034657850
SN - 0041-1337
VL - 69
SP - 1912
EP - 1922
JO - Transplantation
JF - Transplantation
IS - 9
ER -