Presidential & Awards Session

Introduction: Recipient CD4 T cells can recognise intact alloantigen “directly” on donor antigen presenting cells (APCs) or processed alloantigen presented “indirectly” by recipient APCs. The direct and indirect alloresponses likely dominate the early and late transplant responses respectively, although the relative longevity of the pathways has not been formally examined. Methods: The duration of direct and indirect allorecognition was assessed by comparing division of adoptively transferred monoclonal populations of CFSElabelled TCR-transgenic CD4 T cells in B6 recipients of mouse cardiac allografts. Direct allorecognition was examined by transfer of ABM CD4 T cells (I-Abm12-reactive) into recipients of bm12 heart grafts. Indirect allorecognition was examined by transfer of: (1) TCR75 CD4 T cells into recipients of B6.Kd hearts (responses against Kd-derived MHCI allopeptide); (2) TEa CD4 T cells into recipients of I-E+veI-A-ve B6 hearts (responses against I-E-derived MHCII allopeptide) and; (3) Mar CD4 T cells into female recipients of male B6 hearts (responses against minor H-Y alloantigen). All 4 allorecognition pathways were additionally examined concurrently in female B6 recipients of male bm12.kd.IE+veI-A-ve allografts. Results: ABM CD4 T cells divided extensively after early adoptive transfer but only minimally when transferred 5 weeks after transplant, in keeping with a self-limiting direct alloresponse. Similarly, indirect pathway anti-MHCII alloresponses were readily apparent early after transplant but were surprisingly undetectable by five weeks, presumably due to diminished late MHCII antigen availability. In contrast, indirect anti-MHCI alloresponses were equally strong at both time points, while the indirect alloresponse against minor H-Y antigen was present but less marked at late time points. Conclusion: Our results confirm the transience of the direct alloimmune response, but unexpectedly highlight that the indirect alloresponse against MHCII is transient while that against MHCI and minor alloantigens persist late after transplantation.