Dendritic Cells in Transplantation—Friend or Foe?

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Dendritic Cells in Transplantation—Friend or Foe? Robert Lechler, Wan Fai Ng, Ralph M. Steinman  Immunity  Volume 14, Issue 4, Pages 357-368 (April 2001) DOI: 10.1016/S1074-7613(01)00116-9

Figure 1 Distribution and Migration of Dendritic Cells (1) Proliferating DC progenitors in the bone marrow release precursor and immature forms of DC into the blood. (2) Precursors to DC in the blood migrate to peripheral tissues. (3) Immature DC capture pathogens and self-antigens from the tissue. (4) Antigen-loaded DC enter afferent lymphatics or the blood and thereby migrate to secondary lymphoid tissue; this process may be accompanied by maturation upon receipt of appropriate stimuli. (5) Tissue DC present MHC-peptide (black circles) complexes to antigen-specific T cells in the secondary lymphoid organs Immunity 2001 14, 357-368DOI: (10.1016/S1074-7613(01)00116-9)

Figure 2 Direct and Indirect Allorecognition (Indirect allorecognition) Alloantigens are shed from the donor cell surface or are taken up as dying allogeneic cells by host antigen-presenting cells (e.g., immature DCs). In the latter, peptides derived from allogeneic MHC molecules are re-presented on the self-MHC molecules (black circles), especially MHC class II, of the recipient antigen-presenting cells, much like conventional antigens. Helper cells recognizing donor MHC class I or II peptides on responder MHC then help the formation and function of CD8+ CTL that directly recognize donor allogeneic MHC molecules (e.g., by releasing IL-2 or other cytokines). (Direct allorecognition) Recipient T cells engage with complexes of intact allogeneic MHC molecules and bound peptides (striped circles) on the surface of donor cells Immunity 2001 14, 357-368DOI: (10.1016/S1074-7613(01)00116-9)

Figure 3 Roles of Donor and Recipient Dendritic Cells in Direct and Indirect Allorecognition (1) The graft contains donor DCs (black) as well as recipient immature DCs (white). (2) Recipient DCs that have captured antigens from the graft (e.g., dying cells) enter the lymph, much like donor graft-derived DCs. (3) In the recipient lymph nodes, donor DCs and recipient DCs can stimulate the direct and indirect pathways of allorecognition. In addition, donor DCs can die in the lymph node, and their MHC products can be processed widely by the recipient DCs. (4) As a result of (3), many more recipient DCs in the lymph nodes are able to capture and present donor peptides to indirect allospecific recipient T cells Immunity 2001 14, 357-368DOI: (10.1016/S1074-7613(01)00116-9)