VISUALIZATION OF THE IN VIVO GENERATION OF DONOR ANTIGEN-SPECIFIC EFFECTOR CD8+ T CELLS DURING MOUSE CARDIAC ALLOGRAFT REJECTION

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Abstract
Background. An adoptive transfer system was used to study the fate of alloreactive CD8+ H-2Kb-specific TCR transgenic (DES+) T cells in vivo after transplantation. Methods. A trace population of 2.0×106 CD8+DES+ T cells were adoptively transferred into syngeneic CBA.Ca (H-2k) mice 24 hr before transplantation of an H-2Kb+ or H-2Kb- cardiac allograft. Results. H-2Kb specific T cells proliferated and produced interleukin-2 and interferon-γ in response to H-2Kb+, but not H-2Kb- cardiac allografts. CD8+DES+ T cells that infiltrated the H-2Kb+ cardiac allografts developed a distinct cell surface and cytokine phenotype compared with the CD8+DES+ T cells that remained in the periphery. H-2Kb-specific graft infiltrating T cells (a) underwent a larger number of cell divisions (>=3), (b) increased in size, (c) up-regulated CD69, and (d) down-regulated CD62L. Conclusions. These results demonstrate that alloantigen-specific T cells can be monitored in vivo during the immune response to an allograft and that the fate of CD8+ T cells specific for the allogeneic class I molecules expressed by the graft is different between cells in the periphery and those that infiltrate the graft.