Sentences with phrase «corneal allograft»

Development of DTH responses to donor alloantigens has been correlated with corneal allograft rejection.

This study examined the role of CD4 + T cell - independent mechanisms of corneal allograft rejection.

The results reported here reaffirm previous findings indicating that T cells are absolutely required for corneal allograft rejection in the mouse (3).

Both CD8 − and CD8 + T cells from CD4 KO corneal allograft rejector mice mediated corneal allograft rejection following adoptive transfer to nude mice.

The capacity of CD8 + T cells to mediate corneal allograft rejection could have been due to the CTL population that might have been present in the CD8 + T cell suspensions used in the adoptive transfer inocula.

The role of DN T cells in corneal allograft rejection was confirmed in two separate in vitro assays in which CD8 − cells were isolated from CD4 KO donors that had rejected corneal allografts and were found to induce apoptosis of donor - specific corneal cells.

The present findings are derived from studies using CD4KO mice and thus, raise the question as to whether the CD4 + T cell - independent immune mechanisms in CD4 KO mice differ from those involved in corneal allograft rejection in wild - type mice whose CD4 + T cells population have been depleted with monoclonal antibodies.

Although the immune basis for corneal allograft rejection was formally established in experimental animals by Maumenee (33) over 50 years ago, the exact immune mechanisms that lead to the corneal graft failure remain poorly understood.

The results of a typical experiment are shown in Figure 3 and demonstrate that even though spleen cells from CD4 KO mice could adoptively transfer corneal allograft rejection, they did not display conventional CTL activity against either BALB / c corneal epithelial or endothelial cells.

An adoptive transfer experiment was performed to confirm that the high incidence of corneal allograft rejection was immune - mediated.

Either of these effector mechanisms might contribute to corneal allograft rejection.

The capacity of CD8 − T cells from CD4 KO donors to mediate corneal allograft rejection is puzzling and on the surface, counterintuitive, since these cells are presumably double negative (DN) T cells.

Tissue - cultured corneal cells were used for in vitro studies rather than the usual lymphoid cells since corneal cells are the relevant target cells in vivo during corneal allograft rejection.

In the present study we sought to determine the role and mechanisms of CD4 - independent rejection of corneal allografts.

Nude mice were challenged with BALB / c corneal allografts one day after the adoptive cell transfers.

However, closer scrutiny of these studies raises questions about the role of CD4 + T cells as the sole mediators of corneal graft rejection, as corneal allografts undergo immune rejection in 33 % of the mice and 64 % of the rats treated with anti-CD4 monoclonal antibody (12, 13) and in 45 % of the CD4 KO mice (14).

BALB / c corneal allografts were transplanted 24 hr later and the fate of the corneal allografts determined.

Interestingly, recipients of CD8 + T lymphocytes failed to mount DTH responses to BALB / c alloantigens (Figure 4), even though similar panels of mice rejected 95 % of their BALB / c corneal allografts (Figure 2B).

Immunohistochemical staining of rejected human corneal allografts has revealed the presence of apoptosis in corneal stromal cells (5).

Spleen cell suspensions were collected 7 — 14 days after CD4 KO mice rejected BALB / c corneal allografts.

By contrast, 71 % (5/7) of the beige nude mice that received spleen cells from CD4 KO mice rejected their BALB / c corneal allografts.

The present demonstration of T cell - mediated apoptosis of allogeneic corneal cells from CD4 KO mice is consistent with previous findings, which noted the presence of apoptotic keratocytes and corneal endothelial cells in rejected corneal allografts in humans and rats respectively (5, 32).

Spleen cells were collected from CD4 KO mice 7 — 14 days after they had rejected BALB / c corneal allografts.

BALB / c corneal allografts underwent rejection in 46 % (6/13; MST = 46 days) of the recipients of CD8 − T lymphocytes and in 95 % (19/20; MST = 15 days) of the recipients of CD8 + T lymphocytes (Figure 2B).

T lymphocytes are required for the rejection of corneal allografts, as athymic, T cell - deficient nude mice do not reject corneal allografts (3).

The CD8 + T cells were already primed, as they were collected from CD4 KO mice that had rejected corneal allografts and thus, may have functioned differently from CD8 + T cells from naïve CD4 KO mice.

Accordingly, spleens were collected from either naïve C57BL / 6 CD4 KO mice or CD4 KO mice that had rejected BALB / c corneal allografts 7 to 14 days earlier.

Indeed, our results indicate that adoptive transfer of CD8 + T cells from CD4 KO mice that had rejected corneal allografts resulted in the rejection of 95 % of the corneal allografts transplanted to athymic recipients.

Histopathological examination of rejected corneal allografts in CD4 KO mice revealed a mixed inflammatory infiltrate containing large numbers of neutrophils and mononuclear cells, which was indistinguishable from the infiltrate seen in rejected corneal allografts in wild - type mice (data not shown).

Several studies suggest that a significant number of corneal allografts undergo rejection in the absence of CD4 + T cells.

CD8 + and CD8 − T cells were collected from either C57BL / 6 mice or adoptive cell transfer recipients one week after the rejection of BALB / c corneal allografts.

However, in vitro assays using spleen cells from CD4 KO mice that had rejected BALB / c corneal allografts failed to detect CTL activity against donor corneal epithelial or endothelial cells.

The results indicated that 54 % (38/70) of the BALB / c corneal allografts underwent rejection in the CD4 KO hosts, while 100 % of the grafts were rejected in wild - type C57BL / 6 mice (Figure 1).

By contrast, adoptive transfer of CD8 − spleens cells from similar donors resulted in the rejection of corneal allografts in almost half of the hosts.

Additional adoptive transfer experiments were performed to ascertain the role of CD8 + and CD8 − T lymphocytes in CD4 - independent rejection of corneal allografts.

None of the ten C57BL / 6 beige nude mice rejected BALB / c corneal allografts (Figure 2A).

BALB / c corneal allografts were transplanted to C57BL / 6 beige nude mice that received either CD8 − or CD8 + T cells from C57BL / 6 CD4 knockout (KO) mice that had rejected BALB / c corneal allografts.

Studies in CD8 knockout (KO) and perforin KO mice demonstrated that CD8 + cytotoxic T lymphocytes (CTL) are unnecessary for the rejection of corneal allografts in mice (8, 9).

Spleen cells were isolated 7 — 14 days after C57BL / 6 CD4 KO mice had rejected BALB / c corneal allografts and were tested for anti - BALB / c CTL in a conventional 4 - hr 51Cr - release assay using BALB / c corneal epithelial and endothelial target cells.

Experiments were performed to confirm that a significant number of corneal allografts underwent rejection in the absence of CD4 + T cells.

Moreover, we have recently shown that interferon - γ (IFN - γ) KO mice, which can not mount classical Th1 immune responses, are nonetheless capable of rejecting corneal allografts (18, 19).