| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
or IL-41
*
Division of Pulmonary Sciences and Critical Care Medicine, and
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences University, Denver, CO 80262
mAb therapy directed against a variety of cell surface accessory
molecules has been effectively utilized to prolong allograft acceptance
in various models of tissue and organ transplantation. The purpose of
this study was to determine whether transient therapy directed against
the adhesion molecule LFA-1 (CD11a) was sufficient to induce
donor-specific tolerance to pancreatic islet allografts. Anti-LFA-1
monotherapy was found to be efficacious in inducing long-term islet
allograft acceptance in multiple donor-recipient strain combinations.
Graft acceptance following anti-LFA-1 therapy was not simply due to
clonal ignorance of donor Ags in that the majority of recipients
bearing established islet allografts resisted rejection induced by
immunization with donor-type APCs. Furthermore, donor-specific
tolerance from anti-LFA-1-treated animals could be transferred to
secondary immune-deficient animals. Taken together, these results
indicated that transient anti-LFA-1 monotherapy resulted in
donor-specific tolerance. In vitro, functionally tolerant animals
retained normal anti-donor reactivity as assessed by proliferative,
cytotoxic, and cytokine release assays that demonstrated that tolerance
was not secondary to general clonal deletion or anergy of
donor-reactive T cells. Finally, anti-LFA-1 treatment was effective
in both IL-4-deficient and IFN-
-deficient recipients, indicating
that neither of these cytokines are universally required for allograft
acceptance. These results suggest that anti-adhesion-based therapy
can induce a nondeletional form of tolerance that is not overtly
dependent on the prototypic Th1 and Th2 cytokines, IFN- and IL-4,
respectively, in contrast to results in other transplantation
models.
This article has been cited by other articles:
|
|
 |
|
  B. Graf, T. Bushnell, and J. Miller LFA-1-Mediated T Cell Costimulation through Increased Localization of TCR/Class II Complexes to the Central Supramolecular Activation Cluster and Exclusion of CD45 from the Immunological Synapse J. Immunol., August 1, 2007; 179(3): 1616 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Murakawa, M. M. Kerklo, M. R. Zamora, Y. Wei, R. G. Gill, P. M. Henson, F. L. Grover, and M. R. Nicolls Simultaneous LFA-1 and CD40 Ligand Antagonism Prevents Airway Remodeling in Orthotopic Airway Transplantation: Implications for the Role of Respiratory Epithelium as a Modulator of Fibrosis J. Immunol., April 1, 2005; 174(7): 3869 - 3879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Moriyama, N. Abiru, J. Paronen, K. Sikora, E. Liu, D. Miao, D. Devendra, J. Beilke, R. Gianani, R. G. Gill, et al. Evidence for a primary islet autoantigen (preproinsulin 1) for insulitis and diabetes in the nonobese diabetic mouse PNAS, September 2, 2003; 100(18): 10376 - 10381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Rayat, Z. A. Johnson, J. N. Beilke, G. S. Korbutt, R. V. Rajotte, and R. G. Gill The Degree of Phylogenetic Disparity of Islet Grafts Dictates the Reliance on Indirect CD4 T-Cell Antigen Recognition for Rejection Diabetes, June 1, 2003; 52(6): 1433 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q.-W. Zhang, D. D. Kish, and R. L. Fairchild Absence of Allograft ICAM-1 Attenuates Alloantigen-Specific T Cell Priming, But Not Primed T Cell Trafficking into the Graft, to Mediate Acute Rejection J. Immunol., June 1, 2003; 170(11): 5530 - 5537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Nicolls, M. Coulombe, J. Beilke, H. C. Gelhaus, and R. G. Gill CD4-Dependent Generation of Dominant Transplantation Tolerance Induced by Simultaneous Perturbation of CD154 and LFA-1 Pathways J. Immunol., November 1, 2002; 169(9): 4831 - 4839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pimenta-Araujo, L. Mascarell, M. Huesca, A. Cumano, and A. Bandeira Embryonic Thymic Epithelium Naturally Devoid of APCs Is Acutely Rejected in the Absence of Indirect Recognition J. Immunol., November 1, 2001; 167(9): 5034 - 5041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Zhou, G. L. Szot, Z. Guo, O. Kim, G. He, J. Wang, M. J. Grusby, K. A. Newell, J. R. Thistlethwaite, J. A. Bluestone, et al. Role of STAT4 and STAT6 Signaling in Allograft Rejection and CTLA4-Ig-Mediated Tolerance J. Immunol., November 15, 2000; 165(10): 5580 - 5587. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
