Masters Theses

Joan E. Bray

Date of Award

3-1988

Degree Type

Thesis

Degree Name

Master of Science

Major

Comparative and Experimental Medicine

Major Professor

John D. Tyler

Committee Members

A.T. Ichiki, D.J. Krahwinkel, M.H. Goldman

Abstract

Miniature swine which have been inbred and defined for their A-0 and MHC antigens (SLA) offer the opportunity to apply immunogenetic analyses of vascular allografts in a large animal model. Accordingly, internal jugular veins were transplanted as interposition grafts to the carotid arteries of 14 unmodified SLA-typed miniature swine. Transplants were performed between size- and age-matched reciprocal pairs sharing zero, one or two haplotypes. Prior to transplantation, pairs were lymphocyte crossmatched (XM) for possible SLA antibody (Ab) and only pairs with a negative XM were used. One week post-transplant and weekly thereafter, recipient sera were XM against donor lymphocytes. Allograft patency (survival) was monitored with a hand-held Doppler immediately post-transplant and then weekly until graft rejection (closure). Two recipients were lost due to post-surgical complications. In MHC matched recipients, only one out of five developed a positive crossmatch (at three weeks). Nevertheless, its graft remained open at 16 weeks and one other recipient's graft remained open at nine weeks. The other MHC matched grafts were rejected at four, seven, and nine weeks (group mean ≥ 9.0 weeks). In the one-haplotype matched group, all recipients developed a positive XM (within six weeks) and all grafts were rejected by week seven (group mean = five weeks). In the two haplotype mismatched group, three of four recipients developed a positive crossmatch (within three weeks) and all grafts were rejected by week four (group mean = 3.5 weeks). Notably, graft rejection invariably occurred coincident with or within two weeks following anti-donor antibody development in MHC mismatched recipients; whereas, in MHC matched recipients, antibody development was rare and showed no connection with graft rejection. Analysis of the data demonstrated the following significant associations: MHC mismatched grafts were rejected an average of 4.3 weeks earlier than matched grafts (p < .02; t-test) and six of seven MHC mismatched recipients developed anti-donor antibody as compared to one of five matched recipients (p = .044; Fisher's exact test). Strong associations were shown when correlating SLA matching and T-cell sensitization. In the completely matched group 50% of the recipients gave a weak MLC response pre-transplant; the mean relative response being 3.5%, which was below the cutoff of 15% for determining positive versus negative results. Post-transplant, this group gave a mean MLR of 21.4%. The 1-haplotype matched group gave a mean relative response of 32.5% pre-transplant and 79.5% post-transplant. All recipients in the completely mismatched group had a positive MLC pre-transplant with a mean of 41.25% which rose to 79% post-transplant. In the completely matched group, 40% of the grafts remained open and had a negative post-transplant MLC. Of the 60% with closed grafts, one-third developed a positive MLC. In the 1-haplotype matched group, all recipients lost their grafts, 50% had a positive pre-transplant MLC, and all had a positive post-transplant MLC. The completely mismatched group had 100% graft closure, and 100% of the recipients gave a positive MLR. These results show there is not a direct correlation between cellular stimulation and graft rejection, although the degree of SLA matching and T-cell response in the MLR have a strong correlation.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS