Selective Targeting of Human Alloresponsive CD8+ Effector Memory T Cells Based on CD2 Expression

Lo, Denise J.; Weaver, T.; Stempora, Linda; Mehta, Aneesh K; Ford, Mandy L.; Larsen, Christian; Kirk, Allan D.

doi:10.1111/j.1600-6143.2010.03317.x

Cited by 124 publications

(159 citation statements)

References 59 publications

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“…Multiple studies have established that early infiltration of CD8 + memory T cells into allografts, such as hearts, kidneys, and livers, facilitates accelerated rejection and presents a barrier to immunosuppression-mediated long-term graft survival (12,(15)(16)(17)(18)(19). Therefore, preclinical studies have focused on targeting this cell population in an effort to improve the survival of solid organ allografts, such as kidneys (17,20,21). However, some reports have indicated that CD8 + T cells with phenotypic and functional characteristics of memory cells can also downregulate immune responses.…”

Section: Introductionmentioning

confidence: 99%

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Krupnick¹,

Lin²,

Li³

et al. 2014

J. Clin. Invest.

115

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Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade-mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8 + T cells (CD44 hi CD62L hi CCR7 + ). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts.

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Section: Introductionmentioning

confidence: 99%

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Krupnick¹,

Lin²,

Li³

et al. 2014

J. Clin. Invest.

115

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“…by our group and others (10)(11)(12)(13)(14)(15)(16). Belatacept is a first-in-class selective costimulation blocker and is clinically indicated as a CNI inhibitor substitute with mycophenolate mofetil and steroids after renal transplantation.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

et al. 2014

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Vascularized composite allotransplantation (VCA) has emerged as a viable limb replacement strategy for selected patients with upper limb amputation. However, allograft rejection has been seen in essentially all reported VCA recipients indicating a requirement for substantial immunosuppressive therapy. Calcineurin inhibitors have served as the centerpiece agent in all reported cases, and CNI-associated complications associated with the broad therapeutic effects and side effects of calcineurin inhibitors have been similarly common. Recently, belatacept has been approved as a calcineurin inhibitor replacement in kidney transplantation, but to date, its use in VCA has not been reported. Herein, we report on the case of a hand transplant recipient who developed recurrent acute rejection with alloantibody formation and concomitant calcineurin inhibitor nephrotoxicity, all of which resolved upon conversion from a maintenance regimen of tacrolimus, mycophenolate mofetil and steroids to belatacept and sirolimus. This case indicates that belatacept may be a reasonable maintenance immunosuppressive alternative for use in VCA, providing sufficient prophylaxis from rejection with a reduced side effect profile, the latter being particularly relevant for nonlife threatening conditions typically treated by VCA.

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“…A kostimuláció bénításán keresztül poszttranszplantációs immunszuppressziós alkalmazásának kipróbálása a fázis II klinikai kísérleteknél tart, ezek eredménye mostanában várható [9]. Főemlősökben végzett kísérletek során igazoló-dott, hogy az alefacept kiiktatja a memória-T-sejteket, CD28 és CD2 kombinált blokádjával teljes allog raft rejekció prevenciót tudtak elérni [23,24].…”

Section: Cd154-cd40 úTunclassified

Recent options in drug therapy after solid organ transplantation

2012

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A szervtranszplantáció ötvenéves történetében az immunszuppresszív terápia fejlődésének köszönhetően egyre jobb szerv-és betegtúlélési eredményekről számoltak be világszerte, azonban a bázisgyógyszereknek minősülő kalcineurin inhibitorok káros mellékhatásait, elsősorban a nephrotoxicitast mellőző vegyületek kifejlesztése csak az elmúlt két évtizedben zajlott. A gazdaszervezet számára idegennek minősülő implantált szerv a recipiensből komplex immunválaszt vált ki. A dolgozatban az immunválasz vázlatos áttekintését követően a szerzők bemutatják az új, eltérő tá-madáspontokon ható gyógyszereket. Ezek vagy már gyakorlati alkalmazásban lévő, vagy rövid időn belül esetlegesen forgalomba kerülő vegyületek, amelyek távlati lehetőségeket nyújtanak a kalcineurin inhibitorok leváltására. Kiemelt hangsúlyt kap a kostimulációs blokádon keresztül ható belatacept és az elmúlt években egyre nagyobb kutatási teret nyerő toleranciaindukció, mint jövőbeli lehetőség. Orv. Hetil., 2012Hetil., , 153, 1294Hetil., -1301. Kulcsszavak: szervátültetés, immunszuppresszió, kalcineurin inhibitor, kostimulációs blokád, toleranciaindukció Recent options in drug therapy after solid organ transplantationSolid organ transplantation has shown improvement in patient and graft survival rates due to the development of immunosuppression in the last fi fty years; however only the last two decades led to the development of new, baseline immunosuppressive drugs that avoid the unlikely side effects of calcineurin inhibitors, especially nephrotoxicity. The transplanted organ is foreign to the host and, therefore, it induces a complex immune response of the recipient. In this review, a brief outline of immune response is given, followed by the introduction of new immunosuppressive drugs acting via variant pathways. These are compounds which are already in use or becoming shortly available and are potential future alternatives for the calcineurin inhibitors. This paper highlights the role of co-stimulation blockade with belatacept and the recently even more intensively studied fi eld of tolerance induction. Orv. Hetil., 2012, 153, 1294-1301 Keywords: organ transplantation, immunosuppression, calcineurin inhibitor, co-stimulation blockade, tolerance induction (Beérkezett: 2012. február 12.; elfogadva: 2012. június 17.) Rövidítések APC = (antigen presenting cell) antigén-bemutató sejt; BKV = BK-vírus; CD = (cluster of differentiation) sejtfelszíni fehérjék jelölése; CMV = cytomegalovirus; CNI = kalcineurin inhibitor; CTLA4 = citotoxikus T-lymphocyta-antigén-4; DC = dentritikus sejt; EBV = Epstein-Barr-vírus; FDA = Food and Drug Administration; FKBP12 = (FK-binding protein 12) FK-kötő fehérje 12; FOXP3 = forkhead boksz p3, egyike a transzkripciós regulátor fehérjéknek; γ-IFN = gamma-interferon; GVH = graft versus host; HUS = hemolitikus urémiás szindróma; IDO = indolamin-2,3-dioxigenáz; IL = interleukin; IL-2R = interleukin-2-receptor; JAK3 = Janus activated kinase 3, citokinreceptorokhoz kötődő tirozinkinázok egyike; LFA-1 = limphocytafunkció-asszociált anti...

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Selective Targeting of Human Alloresponsive CD8+ Effector Memory T Cells Based on CD2 Expression

Cited by 124 publications

References 59 publications

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report.

Recent options in drug therapy after solid organ transplantation

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