Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice.
(2002) In Transplantation 74(1). p.35-41- Abstract
- BACKGROUND: Blockade of CD40 ligand (CD40L; CD154, gp39) is a potential treatment for autoimmune disease and allograft rejection. However, CD40L-/- mice are capable of mobilizing cellular immune responses to viral, parasitic, and intracellular bacterial infections as well as rejecting skin grafts with nearly the same efficiency as wild-type mice. CD40L-deficient mice (CD40L-/-) or wild-type mice treated with anti-CD40L develop chronic vasculopathy only 8 weeks after allogeneic heart transplantation. To overcome CD40L-independent immune responses, we used anti-lymphocyte function-associated antigen monoclonal antibody (LFA)-1, which has previously been shown to inhibit CD8+ immune responses. METHODS: We conducted mixed lymphocyte reactions,... (More)
- BACKGROUND: Blockade of CD40 ligand (CD40L; CD154, gp39) is a potential treatment for autoimmune disease and allograft rejection. However, CD40L-/- mice are capable of mobilizing cellular immune responses to viral, parasitic, and intracellular bacterial infections as well as rejecting skin grafts with nearly the same efficiency as wild-type mice. CD40L-deficient mice (CD40L-/-) or wild-type mice treated with anti-CD40L develop chronic vasculopathy only 8 weeks after allogeneic heart transplantation. To overcome CD40L-independent immune responses, we used anti-lymphocyte function-associated antigen monoclonal antibody (LFA)-1, which has previously been shown to inhibit CD8+ immune responses. METHODS: We conducted mixed lymphocyte reactions, cytotoxicity assays, skin transplantation, and vascularized heterotopic heart transplantation in wild-type B6 and CD40L-deficient mice in the presence and absence of anti-LFA-1 to study the effects of anti-LFA-1 in the absence of CD40L signaling. RESULTS: Anti-LFA-1 inhibited proliferation of naïve CD40L-/- mixed leukocyte reactions and the lysis of donor targets by CD40L-/- cytotoxic T lymphocytes. Anti-LFA-1-treated CD40L-/- mice that received fully MHC-mismatched skin grafts showed significant prolongation of graft survival, with a median survival time of 55 days (mean 66 days) compared with 13 and 21 days in wild-type and CD40L-/- controls, respectively. CD40L-/- mice that received fully MHC-mismatched vascularized heart transplants treated with four doses of 200 microg of anti-LFA-1 at the time of transplantation did not develop any signs of chronic vasculopathy 150 days after transplantation. CONCLUSION: These results indicate that anti-LFA-1 can complement CD40L inhibition in the prevention of undesirable immune responses. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/109519
- author
- Corbascio, Matthias ; Mahanty, Harish ; Österholm, Cecilia LU ; Qi, Zhongquan LU ; Pearson, Thomas C ; Larsen, Christian P ; Freise, Chris E and Ekberg, Henrik LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Skin Transplantation, Postoperative Complications : prevention & control, Postoperative Complications : immunology, Knockout, Mice, Inbred C57BL, Inbred C3H, Inbred BALB C, Male, Heart Transplantation, Graft Survival : immunology, Graft Rejection : therapy, Chronic Disease, Cell Division : immunology, CD40 Ligand : immunology, CD40 Ligand : genetics, Monoclonal : pharmacology, Antibodies, Graft Rejection : immunology, Animal, Support, Non-U.S. Gov't, T-Lymphocytes, Cytotoxic : cytology, Cytotoxic : immunology, Transplantation, Homologous, Vascular Diseases : immunology, Vascular Diseases : prevention & control, Vascular Diseases : therapy
- in
- Transplantation
- volume
- 74
- issue
- 1
- pages
- 35 - 41
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000176998100007
- pmid:12134096
- scopus:0037099419
- ISSN
- 1534-6080
- language
- English
- LU publication?
- yes
- id
- dd13fc0b-f6c1-4315-9b86-b1193007c24c (old id 109519)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12134096&dopt=Abstract
- date added to LUP
- 2016-04-01 15:31:24
- date last changed
- 2022-01-28 05:43:41
@article{dd13fc0b-f6c1-4315-9b86-b1193007c24c,
abstract = {{BACKGROUND: Blockade of CD40 ligand (CD40L; CD154, gp39) is a potential treatment for autoimmune disease and allograft rejection. However, CD40L-/- mice are capable of mobilizing cellular immune responses to viral, parasitic, and intracellular bacterial infections as well as rejecting skin grafts with nearly the same efficiency as wild-type mice. CD40L-deficient mice (CD40L-/-) or wild-type mice treated with anti-CD40L develop chronic vasculopathy only 8 weeks after allogeneic heart transplantation. To overcome CD40L-independent immune responses, we used anti-lymphocyte function-associated antigen monoclonal antibody (LFA)-1, which has previously been shown to inhibit CD8+ immune responses. METHODS: We conducted mixed lymphocyte reactions, cytotoxicity assays, skin transplantation, and vascularized heterotopic heart transplantation in wild-type B6 and CD40L-deficient mice in the presence and absence of anti-LFA-1 to study the effects of anti-LFA-1 in the absence of CD40L signaling. RESULTS: Anti-LFA-1 inhibited proliferation of naïve CD40L-/- mixed leukocyte reactions and the lysis of donor targets by CD40L-/- cytotoxic T lymphocytes. Anti-LFA-1-treated CD40L-/- mice that received fully MHC-mismatched skin grafts showed significant prolongation of graft survival, with a median survival time of 55 days (mean 66 days) compared with 13 and 21 days in wild-type and CD40L-/- controls, respectively. CD40L-/- mice that received fully MHC-mismatched vascularized heart transplants treated with four doses of 200 microg of anti-LFA-1 at the time of transplantation did not develop any signs of chronic vasculopathy 150 days after transplantation. CONCLUSION: These results indicate that anti-LFA-1 can complement CD40L inhibition in the prevention of undesirable immune responses.}},
author = {{Corbascio, Matthias and Mahanty, Harish and Österholm, Cecilia and Qi, Zhongquan and Pearson, Thomas C and Larsen, Christian P and Freise, Chris E and Ekberg, Henrik}},
issn = {{1534-6080}},
keywords = {{Skin Transplantation; Postoperative Complications : prevention & control; Postoperative Complications : immunology; Knockout; Mice; Inbred C57BL; Inbred C3H; Inbred BALB C; Male; Heart Transplantation; Graft Survival : immunology; Graft Rejection : therapy; Chronic Disease; Cell Division : immunology; CD40 Ligand : immunology; CD40 Ligand : genetics; Monoclonal : pharmacology; Antibodies; Graft Rejection : immunology; Animal; Support; Non-U.S. Gov't; T-Lymphocytes; Cytotoxic : cytology; Cytotoxic : immunology; Transplantation; Homologous; Vascular Diseases : immunology; Vascular Diseases : prevention & control; Vascular Diseases : therapy}},
language = {{eng}},
number = {{1}},
pages = {{35--41}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Transplantation}},
title = {{Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice.}},
url = {{http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12134096&dopt=Abstract}},
volume = {{74}},
year = {{2002}},
}