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Index A mechanisms, 240–243 Accommodation mouse models induction, 248 acute rejection, 112–113 mouse models, 114–115 chronic rejection, 113–114 Acute rejection hyperacute rejection, 112 B-cell role, 56–58 prevention biomarkers, 46–49 accommodation induction, 248 chemokines, 43–45, 52 antibody or antibody-producing cell innate immunity, 52–54, 245–247 removal, 248 antigen removal, 247 kidney transplantation, 344–346 B-cell tolerance induction, 248 mouse models complement cascade prevention, 247–248 antibody-mediated rejection, 112–113 Antilymphocyte serum (ALS), history of use, 13 heart transplantation, 109–110 Antithymocyte globulin (ATG) kidney transplantation, 110–111 immunosuppression induction, 95–96 skin transplantation, 108–109 primate model use, 132–133, 145 overview, 41–42 ATG . See Antithymocyte globulin T-cell role ATRA. See All-trans retinoic acid activation, 54–56 Azathioprine memory T cells, 56 immunosuppression maintenance, 97 regulatory T cells, 55 primate model use, 128 AEB-071. See Sotrastaurin Alefacept, immunosuppression therapy, 102 Alemtuzumab B immunosuppression induction, 96–97 B cell. See also Antibody-mediated rejection; lymphocyte depletion, 146 Lymphocyte depletion Allogeneic response. See also Rejection acute rejection role, 56–58 allogeneic nonself, 30 allogeneic response, 35, 37 B cell, 35, 37 allograft rejection role, 43 graft endothelium role, 36–37, 54 mesenchymal stromal cell interactions with innate immune cells, 32–33, 35–36 allogeneic cells, 231–232 overview, 29–30 tolerance induction, 248 prospects for study, 37 Basiliximab, immunosuppression induction, 96 T cell b-Cell transplantation. See Islet transplantation; alloreactivity, 30–32 Pancreas transplantation T-cell receptor gene rearrangement, 31 Betacept, immunosuppression maintenance, types in transplanted organ recognition, 34–35 99–100 All-trans retinoic acid (ATRA),regulatory T-cell stability Billingham, Rupert, 6–8, 259 effects, 194 Bioethics. See Ethics, transplantation ALS. See Antilymphocyte serum BK virus, kidney transplantation infection, AMR. See Antibody-mediated rejection 349–350 Antibody-mediated rejection (AMR) Bortezomib, immunosuppression therapy, 101 acute humoral response, 57–58 complement role, 81–82 epitopes, 241–243 C heart transplantation, 321–322 Calne, Roy, 9–10 kidney transplantation, 345–346 Campath-1H. See Alemtuzumab macrophage role, 53–54 CAN. See Chronic allograft nephropathy 421 Index Cancer. See also Posttransplantation antibodies, 60–61 lymphoproliferative disease antibody-mediatedrejectionmousemodels,113–114 guidelines for transplantation by cancer type, 386 biomarkers, 49–50 kidney transplant patient management, 394–395 endothelial cell role, 60–61 preexisting cancer fibrosis, 61–62 deceased donors, 385, 387–388 histological lesions, 59–60 organ donors, 384–385 human leukocyte antigen antibodies, 61 transplant recipients, 381–382 mechanisms, 58–59 risk overview, 42 classification, 387 CLAD. See Chronic lung allograft dysfunction immunosuppression regimens, 391–392 CMV. See Cytomegalovirus organ transplantation and cancer types, 389–390 Complement screening in transplant recipients antibody-mediated rejection role, 81–82 breast cancer, 393 antibody-mediated rejection therapeutic targeting, cervical cancer, 393 247–248 colon cancer, 394 C3 activation, 76–77 renal cancer, 394 cascade, 78 skin cancer, 394 cell-mediated graft rejection role, 80–81 survival in transplant recipients, 392–393 inflammatory injury mediation shortly after transmission by type, 387 transplantation, 77, 79–80 viral infection in carcinogenesis after ischemia–reperfusion injury role, 77, 79, 87 transplantation, 390–391 mesenchymal stromal cell response, 227 Carrel, Alexis, 2–4, 407–408 Toll-like receptor pathway cross talk, 86 CCR2, allograft rejection role, 45 Costimulatory blockade. See also specific molecules CCR4, allograft rejection role, 45 clinical studies CCR5, allograft rejection role, 43–44 CD154 antibody, 183 CCR7, allograft rejection role, 45 CTLA-4 antibody, 183–184 CD3 immunotoxin, lymphocyte depletion, 135, 147 off-target effects, 267 CD28, costimulatory blockade, 130, 177–179, peripheral tolerance induction, 116 184–185, 265 primate models CD40, costimulatory blockade, 180–181, 185, CD154 antibody, 182–183 249, 265–266 CTLA-4 antibody, 130–131, 182 CD40 L. See CD154 prospects CD58. See LFA-3 activation of inhibitors, 185 CD134. See OX40 CD154/CD40, 185 CD137. See 4-1BB CD28 blockade, 184–185 CD154 (CD40 L), costimulatory blockade, 131, LFA-3, 185–186 180–183, 185, 249, 265–266 systemic immunosuppression, 249 Chimerism, tolerance induction targets clinical studies of mixed chimerism, 164–166, CD28/CTLA-4, 177–179 252–263 CD40/CD154, 180–181, 265–266 history of study, 14–16 inducible T-cell costimulator, 179–180 mechanism of mixed chimerism induction, 166–169 OX40, 181/4-1BB, 181–182 mouse model studies programmed death 1 receptor, 180 lymphocyte depletion, 158–159 transgenic animal studies, 249 mixed chimerism, 160 CP-690550. See Tofacitinib pig studies of mixed chimerism, 164–166, 252–263 CRM9, lymphocyte depletion, 147 primate models CsA. See Cyclosporine central tolerance with mixed chimerism, CTLA-4 115–116, 163–164 costimulatory blockade peripheral tolerance with costimulatory activation of inhibitors, 185 blockade, 116 clinical studies, 183–184 prospects for study, 169–170 overview, 177–179, 265 Chronic allograft nephropathy (CAN), 58–59 peripheral tolerance induction, 116–117 Chronic lung allograft dysfunction (CLAD), 313–314 primate model studies, 130–131, 182 Chronic rejection regulatory T-cell function, 196 422 Index CXCR3, allograft rejection role, 44–45 recipient equity and organ distribution fairness, Cyclosporine (CsA) 402–404 history of use, 13–14 Everolimus, immunosuppression maintenance, 99 immunosuppression maintenance, 98 primate model use, 129 F Cytomegalovirus (CMV) lymphocyte depletion association, 149 Facial transplantation opportunistic infection, 372, 377–380 complications, 364–366 prophylaxis, 378 immunosuppression, 363–364 outcomes motor function, 359–362 D nerve sensitivity, 359 Daclizumab, immunosuppression induction, 96 patient satisfaction, 363 DC. See Dendritic cell peripheral nerve regeneration and cortical Delayed graft function (DGF), kidney, 343–344 integration, 360, 363 Dempster, William, 4–5 overview, 355–356 Dendritic cell (DC) primate models, 128 acute rejection role, 54 prospects, 366 allogeneic response, 33, 35–36 rejection, 364 allograft rejection role, 42–43 surgical technique, 356–358 mesenchymal stromal cell modulation, Fibrosis, chronic rejection, 61–62 229–230 Fingolimod (FTY720), primate model use, 130, 146 plasmacytoid dendritic cell hypothesis of tolerance 4-1BB (CD137), costimulatory blockade, 181–182 induction Foxp3, regulatory T-cell induction, 192–193 kidney transplantation, 325 FTY720. See Fingolimod liver transplantation, 326 DGF. See Delayed graft function G Diabetes. See also Islet transplantation; Pancreas GATA3, 199 transplantation Gibson, Thomas, 5–6 complications, 289–293 Glucocorticoids, immunosuppression maintenance, islet transplantation, 25 97–98 kidney transplantation, 23–24 Graft-versus-host disease (GVHD) renal failure progression, 289 chimerism studies, 133–134 Donald, Hugh, 6 hematopoietic cell transplantation, 158, 266–267 history of study, 8 E mixed chimerism studies in mice, 160 Guthrie, Charles, 3 EBV. See Epstein–Barr virus GVHD. See Graft-versus-host disease Eculizumab, immunosuppression therapy, 101 Endothelial cell acute rejection role, 54 H allograft rejection role, 36–37 Hamburger, Jean, 8–9 chronic rejection role, 60–61 Hand transplantation growth factor receptors in activation, 61 complications, 364–366 Epstein–Barr virus (EBV). See also immunosuppression, 363–364 Posttransplantation outcomes lymphoproliferative disease motor function, 359–362 opportunistic infection, 372, 375, 377–379 nerve sensitivity, 359 Ethics, transplantation patient satisfaction, 363 default to donation policy, 401–402 peripheral nerve regeneration and cortical encouraged volunteerism integration, 360, 363 enforcement, 402 overview, 355–356 inadequacy in organ donation, 400 primate models, 128–129 markets for organs, 400–401 prospects, 366 organ procurement policy, 399–400 rejection, 364 organ rationing and justice, 404–405 surgical technique, 356–358 423 Index HAR. See Hyperacute rejection Human leukocyte antigen. See Major Heart transplantation histocompatibility complex, 61 antibody-mediated rejection, 321–322 Human papillomavirus (HPV), infection in heart/kidney transplantation outcomes, 329–335 carcinogenesis after heart/lung transplantation, 312 transplantation, 391 immunosuppression, 320–321 Human T-cell lymphotropic virus (HTLV), transplant kidney-induced cardiac allograft induction recipient infection, 372–373 overview, 327 Hume, David, 5 primate models, 329 Hunter, John, 6 regulatory T-cell studies Hyperacute rejection (HAR) coculture suppression assays, 328–329 antibody-mediated rejection mouse models, 112 host thymectomy, 328 overview, 41, 240–243 major histocompatibility complex-mis- matched swine, 329 putative intragraft Tregs, 329 I roles ICOS. See Inducible T-cell costimulator donor antigen load, 327–328 IL-2. See Interleukin-2 donor kidney irradiation, 328 IL-10. See Interleukin-10 donor nephrectomy, 328 IL-35. See Interleukin-35 mouse models of acute rejection, 109–110 Immune reconstitution syndrome (IRIS), 380 organ preservation, 322 Immunosuppression. See also Costimulatory blockade; outcomes, 322 Opportunistic infection; specific drugs overview,
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