**3.1 T-cell mediated rejection**

404 Chronic Kidney Disease

direct pathway where recipient dendritic cells acquire intact allogeneic MHC–peptide complexes from donor cells and present them to recipient T cells. (Harrera et al., 2004; Lechlar and Batchelar, 1982; Warrens et al., 1994). In the context of transplantation, while the direct and the indirect pathways are well recognized and understood, the semi-direct

pathway is not known to be of clinical importance in allograft rejection. (Figure 1)

Fig. 1. Mechanism of antigen presentation in the direct and indirect pathways.

context of chronic graft failure.

As far as the direct pathway is concerned, if the immunological milieu is left unaltered, a strong and effective alloresponse would follow primarily due to the very high number of recipient T-cells that will recognize the transplant tissue as foreign. Due to the nature of this mechanism, this pathway is of primary importance in the immediate post transplant period. T-cell depletion using various immunosuppressive regimens, including induction protocols, severely compromises this process. Another phenomenon observed is depletion of donor derived dendritic cells through apoptosis and elimination by recipient immune reactivity. This is also accompanied by a decline in the number of recipient T cells with direct antidonor allospecificity with time, most pronounced in the CD4+ CD45RO+ (memory) subset (Hornick et al, 1998). However, this decline in direct pathway responses with time is as pronounced in patients with chronic rejection as in those with stable graft function and this supports the view that the direct pathway of allorecognition is of little importance in the

As the direct pathway declines with time, recipient dendritic and other antigen presenting cells travel through the graft, picking up soluble MHC alloantigens or antigens derived from donor cells and present them to T-cells activating CD4 + and CD 8+ cells (the indirect pathway) (Auchincloss et al. , 1993; Kievits et al.,1991). The predominant antigen presentation is done through MHC-Class II cells which have an affinity towards the CD4+ Acute T-cell mediated rejection (Type/Grade)


Chronic T-cell mediated rejection

'Chronic allograft arteriopathy' (arterial intimal fibrosis with mononuclear cell infiltration in fibrosis, formation of neo-intima)

Fig. 2. Infiltration of tubules and interstitium with T cells (*Courtesy of Suzanne Meleg-Smith, MD.*)
