The diversity of alloreactive T cells in graft rejection and the presence of extensive crossreactivity among alloreactive T cells indicate that the induction of transplantation tolerance may fundamentally alter the size of host T-cell repertoire involved in protective immunity and immune surveillance, especially those that are crossreactive to conventional antigens. We herein highlight the crossreactive nature of alloreactive T cells and the potential risks of altered T-cell repertoire associated with the induction of transplantation tolerance. The possibility that T-cell tolerance to one set of antigens results in their tolerance to other unrelated antigens due to T-cell crossreactivity and/or heterogeneity is defined as ‘cross-immune tolerance’. The definition and significance of this concept were discussed in details.