title: Effect of streptavidin on cardiac allograft prolongation is due to host T-Cell suppression.
abstract: OBJECTIVE
  The aim of this study was to evaluate the effectiveness of streptavidin immunomodulation in the high-responder WF-to-Lewis combination.
  
  
  RESULTS
  We examined the effects of streptavidin on the proliferative response of T cells in coculture studies. Two to 200 microg/mL streptavidin significantly (P < .001) suppressed the proliferation of Lewis T cells to WF by 76%-83% compared with untreated responders. Next, we studied the survival of WF cardiac allografts in Lewis recipients pretreated with streptavidin. A 5-day course of peritransplantation recipient treatment with streptavidin doses of 8, 12, 20, 40, and 60 mg/kg combined with single dose of 0.5 mL antilymphocyte serum (ALS) significantly (P < .001) prolonged cardiac allograft survival from MST of 7 +/- 0.5 and 8 +/- 0.5 days in naive and ALS-treated controls to 15 +/- 1, 20 +/- 3, 16 +/- 3, 17 +/- 3, and 23 +/- 2 days, respectively. In contrast, posttransplantation administration of 80 mg/kg streptavidin resulted in animal death, suggesting toxicity of this dose. Additionally, 10 mg/kg or 20 mg/kg streptavidin administration for 10 consecutive days resulted in significant graft prolongation (MST of 18 +/- 1 and 21 +/- 1 days, respectively; P < .001).
  
  
  CONCLUSIONS
  Although peritransplantation streptavidin treatment is effective in prolonging rat cardiac allografts in the high-responder WF-to-Lewis combination, it does not induce permanent graft survival as observed in the low-responder combination of Lewis-to-ACI. Our finding of in vitro immunomodulatory effect of streptavidin on T-cell proliferation suggests that its in vivo effect is partly due to prevention of T-cell activation following antigen exposure.
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. pw2004@columbia.edu
authors.forename: P
authors.initials: P
authors.lastname: Witkowski
authors.forename: R A
authors.initials: RA
authors.lastname: Fawwaz
authors.forename: M X
authors.initials: MX
authors.lastname: Jin
authors.forename: H A
authors.initials: HA
authors.lastname: DePaz
authors.forename: O O
authors.initials: OO
authors.lastname: Oluwole
authors.forename: M A
authors.initials: MA
authors.lastname: Hardy
authors.forename: S F
authors.initials: SF
authors.lastname: Oluwole
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017710:Lymphocyte Transfusion; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D013154:Spleen / Q000276:immunology / Q000528:radiation effects; D019809:Streptavidin / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019809:Streptavidin