title: CD28 blockade induces division-dependent downregulation of interleukin-2 receptor alpha.
abstract: BACKGROUND
  Blockade of T cell costimulatory molecules represents a promising new method of attenuating donor-reactive T cell responses to promote graft survival following transplantation. However, recent studies in murine models have shown the presence of an initial high frequency of naïve donor-reactive T cells may render this strategy ineffective.
  
  
  METHODS
  In this report, we examined the phenotypic changes associated with CD28 blockade on T cells stimulated at increasing precursor frequencies in vitro.
  
  
  RESULTS
  We found that treatment with the CD28 blocker CTLA-4 Ig resulted in downregulation of the alpha chain of the IL-2 receptor (CD25) in a division-dependent manner. Significantly, blockade of the CD28 pathway was more effective in down-regulating CD25 when the donor-reactive T cell population was present at low as compared to high precursor frequency.
  
  
  CONCLUSIONS
  These results imply that treatment with CD28 blockers and anti-CD25 mAbs may cooperate in promoting graft survival under conditions of low MHC matching where the donor-reactive T cell precursor frequency is high.
authors.affiliation: Emory Transplant Center and Department of Surgery, Emory University, Atlanta, GA 30079, United States. mandy.ford@emory.edu
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ford
authors.forename: Linda L
authors.initials: LL
authors.lastname: Stempora
authors.forename: Christian P
authors.initials: CP
authors.lastname: Larsen
mesh_terms: D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006085:Graft Survival / Q000276:immunology; D018796:Immunoconjugates / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D018796:Immunoconjugates; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D000069594:Abatacept