[摘要]：Background. Induction with lymphocyte-depleting antibodies is routinely used to prevent rejection but often skews T cells toward memory. It is not fully understood which memory and regulatory T-cell subsets are most affected and how they relate to clinical outcomes. Methods. We analyzed T cells from 57 living-donor renal transplant recipients (12 reactive and 45 quiescent) 2.8 +/- 1.4 years after alemtuzumab induction. Thirty-four healthy subjects and nine patients with acute cellular rejection (ACR) were also studied. Results. We found that alemtuzumab caused protracted CD4 more than CD8 T-lymphocyte deficiency, increased proportion of CD4(+) memory T cells, and decreased proportion of CD4(+) regulatory T cells. Reactive patients exhibited higher proportions of CD4(+) effector memory T cells (T-EM) and CD8(+) terminally differentiated T-EM (T-EM RA), with greater CD4(+) T-EM and CD8(+) T-EM RA to regulatory T cell ratios, than quiescent patients or healthy controls. Patients with ongoing ACR had profound reduction in circulating CD8(+) T-EM RA. Mixed lymphocyte assays showed significantly lower T-cell proliferation to donor than third-party antigens in the quiescent group, while reactive and ACR patients exhibited increased effector molecules in CD8(+) T cells. Conclusions. Our findings provide evidence that T-cell skewing toward T-EM may be associated with antigraft reactivity long after lymphodepletion. Further testing of T-EM and T-EM RA subsets as rejection predictors is warranted.
