FREQUENCY OF ALLOANTIGEN-SPECIFIC T CYTOTOXIC CELLS IN HIGH- AND LOW-RESPONDER RECIPIENTS OF CLASS I MHC-DISPARATE HEART ALLOGRAFTS

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Abstract
Presentation of an isolated class I antigeneic disparity to PVG.1U (RT1u) high-responder recipients resulted in rapid PVG.R8 (RT1.AaBuDuCu) heart allograft rejection with a median survival time (MST) of 8.25 days, but indefinite PVG.R1 (RT1.AaBcDcCc) heart allograft survival in PVG (RT1c) low-responder recipients. (PVG.R8xPVG.1U)F1 heart allografts, which express half the RT1.Aa-encoded molecules present on PVG.R8 hearts, were rejected within an MST if 14.75 days by PVG.1U recipients. Despite these two vivo differences, normal PVG.1U rats display a frequency of anti-RT1.Aa-directed T cytotoxic (fTc) cells of 1:990 in spleen and 1:1240 in LN, which are similar to the fTc found in low-responder PVG rats of 1:950 in spleen and 1:1423 in LN. One day 5 postgrafting, PVG.1U recipients of PVG.R8 hearts showed an increased fTc within graft-infiltrating T cells to 1:151, and within spleen to 1:527, but the fTc remained unchanged in LN (1:1310). Either 30 or 100 days after PVG.R8 heart allograft rejection, PVG.1U rats displayed an increased fTc in spleen (1:405) but the fTc in LN remained unchanged (1:1165). In contrast, low-responder PVG recipients that bore functional PVG.R1 heart allografts revealed no change in the splenic fTc on day 5 (1:2073) or on day 14 (1:1246) postgrafting. Additional in vitro experiments revealed further differences between high and low responders: both purified sensitized W3/25+ (CD4) and OX8+ (CD8) T cells obtained from the high PVG.1U, but not the low PVG responder strain, proliferated well in MLR culture in response to class I alloantigens. These findings suggest that the W3/25+ T cell population may participate in the induction of rejection in high-responder PVG.1U rats.