Limits...
A crucial role of IL-17 and IFN-γ during acute rejection of peripheral nerve xenotransplantation in mice.

Yu X, Jiang Y, Lu L, Gong X, Sun X, Xuan Z, Lu L - PLoS ONE (2012)

Bottom Line: However, xenotransplant rejection is severe with cellular immunity, and Th1 cells play an important role in the process.The changes of IL-4 level had no significant difference between xenotransplanted group and sham control group.These data suggest that Th17 cells contribute to the acute rejection process of peripheral nerve xenotransplant in addition to Th1 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hand Surgery, First Hospital, Jilin University, Changchun, China.

ABSTRACT
Nerve injuries causing segmental loss require nerve grafting. However, autografts and allografts have limitations for clinical use. Peripheral nerve xenotransplantation has become an area of great interest in clinical surgery research as an alternative graft strategy. However, xenotransplant rejection is severe with cellular immunity, and Th1 cells play an important role in the process. To better understand the process of rejection, we used peripheral nerve xenografts from rats to mice and found that mononuclear cells expressing IFN-γ and IL-17 infiltrated around the grafts, and IFN-γ and IL-17 producing CD4+ and CD8+ T cells increased during the process of acute rejection. The changes of IL-4 level had no significant difference between xenotransplanted group and sham control group. The rejection of xenograft was significantly prevented after the treatment of IL-17 and IFN-γ neutralizing antibodies. These data suggest that Th17 cells contribute to the acute rejection process of peripheral nerve xenotransplant in addition to Th1 cells.

Show MeSH

Related in: MedlinePlus

Xenotransplant after using IFN-γ and IL-17 neutralizing antibodies respectively.(A) Spleens were collected at each time point (1, 3, 6, 11, 16, and 30 days) from xenotransplanted mice with or without neutralizing antibodies (single used and mixed used) treatment, and used for flow cytometry analysis. The levels of IFN-γ producing CD3+CD8− T cells and IL-17 producing CD3+CD8− T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 compared with the control group. The levels of IFN-γ producing CD3+CD8+ T cells and IL-17 producing CD3+CD8+ T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 and day 6 compared with the control group. (B) Tissues surrounding the xenografts were used to do Immunohistochemical staining to measure the expression of IFN-γ+ and IL-17+ cells. We observed that mononuclear cells invasion significantly decreased at day 3 and day 6; and IFN-γ and IL-17 expression decreased in the recipients with IFN-γ and IL-17 neutralizing antibodies single used and mixed used from day 11 to day 30. *, p<0.05; **, p<0.01; *** p<0.001. (We performed this experiment twice).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3316676&req=5

pone-0034419-g005: Xenotransplant after using IFN-γ and IL-17 neutralizing antibodies respectively.(A) Spleens were collected at each time point (1, 3, 6, 11, 16, and 30 days) from xenotransplanted mice with or without neutralizing antibodies (single used and mixed used) treatment, and used for flow cytometry analysis. The levels of IFN-γ producing CD3+CD8− T cells and IL-17 producing CD3+CD8− T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 compared with the control group. The levels of IFN-γ producing CD3+CD8+ T cells and IL-17 producing CD3+CD8+ T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 and day 6 compared with the control group. (B) Tissues surrounding the xenografts were used to do Immunohistochemical staining to measure the expression of IFN-γ+ and IL-17+ cells. We observed that mononuclear cells invasion significantly decreased at day 3 and day 6; and IFN-γ and IL-17 expression decreased in the recipients with IFN-γ and IL-17 neutralizing antibodies single used and mixed used from day 11 to day 30. *, p<0.05; **, p<0.01; *** p<0.001. (We performed this experiment twice).

Mentions: In order to investigate the role of IFN-γ and IL-17 in peripheral nerve xenotransplantation, we blocked IFN-γ or (and) IL-17 by using neutralizing antibodies before transplantation of rat nerve into the mice. The sera levels of IFN-γ and IL-17 at day 6 were statistically lower in the xenograft recipients with IFN-γ and IL-17 neutralizing antibodies single and mixed used compared with the recipients without antibodies. The levels of both cytokines returned to values of recipients without antibodies by day 11 after transplantation. There was no significant difference between the groups of antibody single used and mixed used. At the same time, we set up another experiment by injection of the neutralizing antibodies one day after xenotransplantation in which we got the consistent outcome that the animals injected the neutralizing antibody before xenotransplantation (Information S1). The levels of IFN-γ producing CD3+CD8+ T cells and IL-17 producing CD3+CD8+ T cells decreased at day 3 and day 6, IFN-γ producing CD3+CD8− T cells, and IL-17 producing CD3+CD8− T cells decreased at day 3 in the recipients with IL-17 neutralizing antibody and mixed used antibodies compared to the levels of recipients without antibodies. Although the level of IFN-γ and IL-17 was lower in the group with mixed used antibodies than the group of IL-17 antibody single used, there was no significant difference between these two groups (Fig. 5A). We observed scattered immunoreactivity for both IFN-γ and IL-17 in the infiltrating mononuclear cells, and found that mononuclear cells invasion decreased at day 3 and day 6; IFN-γ and IL-17 expression decreased in the recipients with IFN-γ and IL-17 neutralizing antibodies single used and mixed used from day 11 after transplantation (Fig. 5B).


A crucial role of IL-17 and IFN-γ during acute rejection of peripheral nerve xenotransplantation in mice.

Yu X, Jiang Y, Lu L, Gong X, Sun X, Xuan Z, Lu L - PLoS ONE (2012)

Xenotransplant after using IFN-γ and IL-17 neutralizing antibodies respectively.(A) Spleens were collected at each time point (1, 3, 6, 11, 16, and 30 days) from xenotransplanted mice with or without neutralizing antibodies (single used and mixed used) treatment, and used for flow cytometry analysis. The levels of IFN-γ producing CD3+CD8− T cells and IL-17 producing CD3+CD8− T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 compared with the control group. The levels of IFN-γ producing CD3+CD8+ T cells and IL-17 producing CD3+CD8+ T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 and day 6 compared with the control group. (B) Tissues surrounding the xenografts were used to do Immunohistochemical staining to measure the expression of IFN-γ+ and IL-17+ cells. We observed that mononuclear cells invasion significantly decreased at day 3 and day 6; and IFN-γ and IL-17 expression decreased in the recipients with IFN-γ and IL-17 neutralizing antibodies single used and mixed used from day 11 to day 30. *, p<0.05; **, p<0.01; *** p<0.001. (We performed this experiment twice).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316676&req=5

pone-0034419-g005: Xenotransplant after using IFN-γ and IL-17 neutralizing antibodies respectively.(A) Spleens were collected at each time point (1, 3, 6, 11, 16, and 30 days) from xenotransplanted mice with or without neutralizing antibodies (single used and mixed used) treatment, and used for flow cytometry analysis. The levels of IFN-γ producing CD3+CD8− T cells and IL-17 producing CD3+CD8− T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 compared with the control group. The levels of IFN-γ producing CD3+CD8+ T cells and IL-17 producing CD3+CD8+ T cells from recipients with IL-17 neutralizing antibody and mixed used antibodies significantly decreased at day 3 and day 6 compared with the control group. (B) Tissues surrounding the xenografts were used to do Immunohistochemical staining to measure the expression of IFN-γ+ and IL-17+ cells. We observed that mononuclear cells invasion significantly decreased at day 3 and day 6; and IFN-γ and IL-17 expression decreased in the recipients with IFN-γ and IL-17 neutralizing antibodies single used and mixed used from day 11 to day 30. *, p<0.05; **, p<0.01; *** p<0.001. (We performed this experiment twice).
Mentions: In order to investigate the role of IFN-γ and IL-17 in peripheral nerve xenotransplantation, we blocked IFN-γ or (and) IL-17 by using neutralizing antibodies before transplantation of rat nerve into the mice. The sera levels of IFN-γ and IL-17 at day 6 were statistically lower in the xenograft recipients with IFN-γ and IL-17 neutralizing antibodies single and mixed used compared with the recipients without antibodies. The levels of both cytokines returned to values of recipients without antibodies by day 11 after transplantation. There was no significant difference between the groups of antibody single used and mixed used. At the same time, we set up another experiment by injection of the neutralizing antibodies one day after xenotransplantation in which we got the consistent outcome that the animals injected the neutralizing antibody before xenotransplantation (Information S1). The levels of IFN-γ producing CD3+CD8+ T cells and IL-17 producing CD3+CD8+ T cells decreased at day 3 and day 6, IFN-γ producing CD3+CD8− T cells, and IL-17 producing CD3+CD8− T cells decreased at day 3 in the recipients with IL-17 neutralizing antibody and mixed used antibodies compared to the levels of recipients without antibodies. Although the level of IFN-γ and IL-17 was lower in the group with mixed used antibodies than the group of IL-17 antibody single used, there was no significant difference between these two groups (Fig. 5A). We observed scattered immunoreactivity for both IFN-γ and IL-17 in the infiltrating mononuclear cells, and found that mononuclear cells invasion decreased at day 3 and day 6; IFN-γ and IL-17 expression decreased in the recipients with IFN-γ and IL-17 neutralizing antibodies single used and mixed used from day 11 after transplantation (Fig. 5B).

Bottom Line: However, xenotransplant rejection is severe with cellular immunity, and Th1 cells play an important role in the process.The changes of IL-4 level had no significant difference between xenotransplanted group and sham control group.These data suggest that Th17 cells contribute to the acute rejection process of peripheral nerve xenotransplant in addition to Th1 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hand Surgery, First Hospital, Jilin University, Changchun, China.

ABSTRACT
Nerve injuries causing segmental loss require nerve grafting. However, autografts and allografts have limitations for clinical use. Peripheral nerve xenotransplantation has become an area of great interest in clinical surgery research as an alternative graft strategy. However, xenotransplant rejection is severe with cellular immunity, and Th1 cells play an important role in the process. To better understand the process of rejection, we used peripheral nerve xenografts from rats to mice and found that mononuclear cells expressing IFN-γ and IL-17 infiltrated around the grafts, and IFN-γ and IL-17 producing CD4+ and CD8+ T cells increased during the process of acute rejection. The changes of IL-4 level had no significant difference between xenotransplanted group and sham control group. The rejection of xenograft was significantly prevented after the treatment of IL-17 and IFN-γ neutralizing antibodies. These data suggest that Th17 cells contribute to the acute rejection process of peripheral nerve xenotransplant in addition to Th1 cells.

Show MeSH
Related in: MedlinePlus