Abstract
Abstract: :
Purpose: To examine the effect of ultraviolet-B (UVB) pre-irradiation of donor corneas in corneal (C) xenografts(X) and allografts(A). Methods: Male Lewis rats (RT1l) received 3mm full-thickness orthotopic CX from male outbred Dunkin Hartley guinea pigs or CA from male DA rats (RTav1). In CX (groups 1-5) the donor graft was either unirradiated (uI) (group1, n=20, CX controls) or pre-irradiated (I) with graded doses of UVB [group 2 (n=8) at 0.1, group 3 (n=13) at 0.2, group 4 (n=8) at 0.3 and group 5 at 0.4 J/cm2 respectively]. In CA groups the donor grafts were either uI (group 6, n=10, CA controls) or I at a dose of 0.2J/cm2. Rejection was defined as an opaque donor cornea. Results: Mean survival times of C grafts were 6.4, 7, 9.5, 10.3, 11.8, 12.8 and >35 days respectively for groups 1 to 7. No survival difference was demonstrated between CX groups 2 and 1 at the 5% level (p=0.1532, logrank test). There were significant differences between groups 3 to 5 compared with group 1 (p<0.0001). There also proved to be a positive correlation of CX survival with UVB dose (p<0.0001, logrank test for trend ). Group 7 CA survived beyond 35 days without signs of rejection, compared with group 6 CA which were all rejected by day 16. Conclusions: UVB irradiation of CA had a profoundly beneficial effect on graft survival believed to result from reduced efficacy of direct antigen (Ag) presentation to the adaptive immune system. The effect of UVB on CX survival was much less marked than for CA. The beneficial effect of UVB on CX survival, presumably also mediated by modified (xeno)Ag presentation, appears inadequate to compete with other elements of host immunity mediating CX rejection. We conclude that although CX rejection is not fully understood, it may be mediated by both adaptive and innate cellular immunity. We have previously ruled out a role for complement in the rejection of CX, and the effect of UVB I reported here is comparable with our observations on the survival of unirradiated CX in T cell depleted recipients. We suggest that CX rejection is mediated largely through innate cellular components of the immune system such as natural killer cells and activated monocytes. This has been shown to be the case for vascularised xenografts in this species combination using recipients with defective humoral and T cell mediated immunity. Further, innate immunity which does not require priming through antigen presentation could explain the tempo of CX rejection seen here.
Keywords: cornea: basic science • immunomodulation/immunoregulation • ACAID