Transplantation in miniature swine: analysis of graft-infiltrating lymphocytes provides evidence for local suppression.
Previous studies from this laboratory have demonstrated that swine tolerant of class I disparate renal allografts show peripheral antidonor cellular reactivity which can be augmented by skin grafting. To assess the possibility of local suppression, cell-mediated lymphocytotoxicity of graft-infiltrating lymphocytes was compared to that of peripheral blood lymphocytes from three tolerant and four acutely rejecting recipients of class I--disparate renal allografts. Mixed lymphocyte cultures using peripheral blood lymphocytes or graft-infiltrating lymphocytes and an equal number of irradiated peripheral blood lymphocyte stimulators were incubated for 6 days and tested in a 6-hr 51Cr release assay. Graft-infiltrating lymphocytes from rejecting animals had potent antidonor cell-mediated lymphocytotoxic activity with or without in vitro stimulation. Anti-third-party reactivity was seen with appropriate stimulation, suggesting heterogeneity of graft-infiltrating lymphocyte cultures. Peripheral blood lymphocytes from rejectors generated donor-specific cell-mediated lymphocytotoxicity. Graft-infiltrating lymphocytes from tolerant animals generated no antidonor cell-mediated lymphocytotoxicity with or without in vitro stimulation, but generated an anti-third-party response. Peripheral blood lymphocytes from tolerant animals displayed both antidonor and anti-third-party reactivity with appropriate in vitro stimulation. These data support the hypothesis that local suppression may contribute significantly to maintenance of tolerance to class I disparate renal allografts in miniature swine.
Rosengard
B R
BR
Transplantation Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kortz
E O
EO
Guzzetta
P C
PC
Sundt
T M
TM
Ojikutu
C A
CA
Alexander
R B
RB
Sachs
D H
DH
D000818:Animals; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D013552:Swine; D013556:Swine, Miniature / Q000276:immunology