De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed

Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8. + T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10. days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8. + T cell development was prevented when CyA was initiated at 0. day or 2. days post-prime (p. <. 0.001), but not 6. days post-prime. Following a boost challenge, these memory CD8. + T cells were capable of producing a similarly sized population of secondary effectors as recipients not treated with CyA (p. >. 0.05). Delaying CyA up to 6. days or later post-prime permits the development of functional de novo allospecific memory CD8. + T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant.