Cell mediated rejection revisited: Past, current, and future directions

The Banff histopathology classification system is the gold standard for assessing the causes of kidney allograft dysfunction triggered by antibody-mediated and T-cell-mediated immune reactions, thereby providing mechanistic insight and guiding therapeutic decisions. The original Banff classification (1993) consisted of four histological categories representing cell-mediated rejection: interstitial inflammation (i), tubulitis (t), endoarteritis (v), and transplant glomerulitis (g). The revised Banff 2007 classification added total inflammation score (ti) from both scarred and unscarred areas based on evolving interpretations of interstitial infiltrates. Further reappraisal of cell-mediated interstitial inflammation led to the introduction of a new inflammation score specific for areas of interstitial fibrosis and tubular atrophy, termed i-IF/TA, in the Banff 2015 scheme, establishment of a new Banff working group on T-cell-mediated rejection (TCMR), and revised criteria of chronic active TCMR in Banff 2017 classification. These Banff scheme updates reflect the general recognition that chronic interstitial inflammation is a common denominator of poor kidney allograft outcome. However, revised theories on the pathogenic importance of interstitial infiltrates have created difficulties in interpretation of chronic tubulointerstitial inflammation, as there are currently no histological criteria to discriminate immune-mediated tissue injury from ‘non-specific’ injury. Evolving theories on vascular lesions, both active and chronic, have also complicated histological assessment by obscuring the distinction between antibody-mediated and T-cell-mediated tissue injury. This review provides an overview of recent ideas on interstitial inflammation and vascular lesions based on emerging concepts of T-cell-mediated rejection.