T cells play an important role in triggering the immune rejection of transplanted tissues. Significant efforts have been made to explore the potential for the induction of donor-specific immune tolerance to achieve long-term graft survival without the need for life-long immunosuppressive therapy. Non-human primates are ideal animal models to test the immune-target tolerance for successful allotransplantation. Recent work done in Dr. Judy Thomas' laboratory has shown that the treatment of rhesus monkeys with anti-CD3-Immunotoxin (IT) resulted in profound T cell depletion, and induced stable tolerance without chronic allograft rejection for up to 3 years. While IT protocol clearly facilitates inducing the tolerance of allografts in macaques, important questions remain to be explored regarding fundamental T cell immunology and future application of the IT strategy to cadaveric transplant tolerance induction in humans. Based on the result demonstrating the ability of macaque repertoires in the macaques depleted of T cells can be restored to various degrees through the thymic-dependent and/or-independent pathways. We also hypothesize that alloantigens may drive the dominant T cell response that is relevant to allograft rejection or tolerance. To test these hypothesis, we will: I. Determine restoration of macaque TCR repertoires following T cell depletion. A. Determine restoration of TCR repertoires in juvenile macaques following T cell depletion. B. Determine restoration of TCR repertoires in old macaques following T cell depletion. II. Assess TCR-based thymic output in young and old macaques after T cell depletion. III. Determine the TCR repertoire in rejected kidney allografts of macaque recipients.

Project Start
2002-09-01
Project End
2003-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
2002
Total Cost
$172,411
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Graham, Melanie L; Rieke, Eric F; Mutch, Lucas A et al. (2012) Successful implementation of cooperative handling eliminates the need for restraint in a complex non-human primate disease model. J Med Primatol 41:89-106
Abouaish, Janine; Graham, Melanie; Bansal-Pakala, Pratima et al. (2011) Successful isolation and transplantation of nonhuman primate islets using a novel purified enzyme blend. Transplantation 92:e40-2
Gansuvd, Balgansuren; Goodwin, Jeanine; Asiedu, Clement K et al. (2008) Invariant natural killer T cells from rhesus macaque spleen and peripheral blood are phenotypically and functionally distinct populations. J Med Primatol 37:1-11
Johnson, J; Pahuja, A; Graham, M et al. (2008) Effects of histone deacetylase inhibitor SAHA on effector and FOXP3+regulatory T cells in rhesus macaques. Transplant Proc 40:459-61
Andrades, P; Asiedu, C K; Gansuvd, B et al. (2008) Pancreatic islet isolation variables in non-human primates (rhesus macaques). Diabetologia 51:1236-44
Asiedu, C; Guarcello, V; Deckard, L et al. (2007) Cloning and characterization of recombinant rhesus macaque IL-10/Fc(ala-ala) fusion protein: a potential adjunct for tolerance induction strategies. Cytokine 40:183-92
Gansuvd, Balgansuren; Asiedu, Clement K; Goodwin, Jeanine et al. (2007) Expansion of CD4+CD25+ suppressive regulatory T cells from rhesus macaque peripheral blood by FN18/antihuman CD28-coated Dynal beads. Hum Immunol 68:478-90
Kim, Geun-Bae; Wang, Zhirui; Liu, Yuan Yi et al. (2007) A fold-back single-chain diabody format enhances the bioactivity of an anti-monkey CD3 recombinant diphtheria toxin-based immunotoxin. Protein Eng Des Sel 20:425-32
Liu, Yuan Yi; Wang, Zhirui; Thomas, Judith et al. (2007) Polymorphisms of CD3epsilon in cynomolgus and rhesus monkeys and their relevance to anti-CD3 antibodies and immunotoxins. Immunol Cell Biol 85:357-62
Asiedu, Clement K; Goodwin, Karen J; Balgansuren, Gansuvd et al. (2005) Elevated T regulatory cells in long-term stable transplant tolerance in rhesus macaques induced by anti-CD3 immunotoxin and deoxyspergualin. J Immunol 175:8060-8

Showing the most recent 10 out of 26 publications