Immunological rationale for induction therapy in patients with donor-specific memory T cells.

The phenomenon of' second set' or ‘accelerated' rejection which characterizes the rapid destruction of a second tissue or organ transplant from the same donor into the same recipient was first described by Medawar and coworkers. Those observations made in untreated recipients were considered as a major evidence for the immunological mechanisms of allograft rejection since such capacity to reject transplants of donor strain origin in an accelerated mode could be transferred to naive recipients by T cells from the presensitized hosts. Cross-reactive grafts from donors sharing MHC class I and/or class II alleles with the sensitizing donor were also rejected in an accelerated fashion, suggesting that accelerated rejection was mediated by sensitized CD4 + and/or CD8 + donor specific alloreactive T cells. The capacity to mount an anamnestic rejection could persist several weeks or months after completion of the first graft rejection, suggesting that memory T cells had been produced following the first transplant. However the mechanisms of memory induction and the phenotypic and functional differences between memory and effector T cells remain controversial. The allograft response entails the clonal expansion of donor MHC class II and MHC class I specific CD4 + and CD8 + T cells, associated with several phenotypic changes, including increased surface expression of CD2 and CD58 (LFA-3), increased affinity of the integrin CD11a/CD18 (LFA-1), de novo expression of the integrin α4β1 (CD29/49d, VLA-4), changes in expression of CD62L and CD44 and decrease of the CD45RA isoform with a compensatory increase of the shorter CD45RO isoform. [ABSTRACT FROM AUTHOR]