Barriers to Transplant Tolerance

Español (soon!) - March 10, 2010

CME on Transplantation is dedicated to online CME conferences, courses and presentations (slides with voice over) on transplantation, given by local and international experts. Its mission is to keep you up-to-date with the most recent developments on transplantation.

Presentation

"Barriers to Transplant Tolerance"
Dr. Laurence A. Turka (biography)
English - 2004-05-18 - 44 minutes

(35 slides)

Summary :
Despite recent successes in inducing allograft tolerance in animal models, robust sustained tolerance in clinical human populations remains elusive. Dr. Laurence Turka discusses why in this presentation on the immunologic barriers to transplant tolerance.

What is the role of different immunosuppressants in facilitating or hampering the induction of tolerance? What is the best way of reducing the alloreactive T cell mass?

Dr. Turka briefly reviews the molecular basis of leukocyte cellular signalling en route to delving into the immunological hurdles that have limited attempts to systematically and consistently induce acceptance of allograft tissues.

Centering his discussion on peripheral methods of inducing tolerance, Dr. Turka reviews the evidence for the effect of blocking the T cell co-stimulatory pathway. The importance of reducing the alloreactive T cell mass in a specific fashion is discussed. Moreover, Dr. Turka introduces his laboratory’s own work on homeostatic T cell proliferation as a barrier to tolerance, as well as the role of heterologous immunity in limiting the application of laboratory models of tolerance to human transplant populations.

Learning objectives :
After viewing this presentation, participants will be able to discuss:
• Cell to cell interactions essential to T cell proliferation
• The effect of blockade of the co-stimulatory pathway on T cells
• The effect of cyclosporine on Tolerance Induction
• The effect of sirolimus on Tolerance Induction
• The effect of non-specific anti-lymphocyte therapy (eg. Campath®) on Tolerance Induction
• The concept of homeostatic proliferation and its effect on tolerance induction
• The concept of heterologous immunity and its effect on tolerance induction

Bibliographic references :
Taylor DK, Neujahr D, Turka LA. Heterologous immunity and homeostatic proliferation as barriers to tolerance. Curr Opin Immunol. 2004 Oct;16(5):558-64.

Chen Y, Heeger PS, Valujskikh A. In vivo helper functions of alloreactive memory CD4+ T cells remain intact despite donor-specific transfusion and anti-CD40 ligand therapy. J Immunol. 2004 May 1;172(9):5456-66.

Adams AB, Williams MA, Jones TR, Shirasugi N, Durham MM, Kaech SM, Wherry EJ, Onami T, Lanier JG, Kokko KE, Pearson TC, Ahmed R, Larsen CP. Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest. 2003 Jun;111(12):1887-95.

Wu Z, Bensinger SJ, Zhang J, Chen C, Yuan X, Huang X, Markmann JF, Kassaee A, Rosengard BR, Hancock WW, Sayegh MH, Turka LA. Homeostatic proliferation is a barrier to transplantation tolerance. Nat Med. 2004 Jan;10(1):87-92. Epub 2003 Nov 30.

Smiley ST, Csizmadia V, Gao W, Turka LA, Hancock WW. Differential effects of cyclosporine A, methylprednisolone, mycophenolate, and rapamycin on CD154 induction and requirement for NFkappaB: implications for tolerance induction. Transplantation. 2000 Aug 15;70(3):415-9.

Kirk AD, Burkly LC, Batty DS, Baumgartner RE, Berning JD, Buchanan K, Fechner JH Jr, Germond RL, Kampen RL, Patterson NB, Swanson SJ, Tadaki DK, TenHoor CN, White L, Knechtle SJ, Harlan DM. Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nat Med. 1999 Jun;5(6):686-93.

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Newsletter 1 (2004-04-08)