Long-term survival of solid organ allografts by brief anti-lymphocyte function-associated antigen-1 monoclonal antibody monotherapy.
Strategies targeting lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule-1 (ICAM-1) have previously been shown to produce long-term survival of solid organ allografts in animals only when both CD11a and ICAM-1 are targeted for a brief (6-7 days) time or when extended (14 weeks) treatment with anti-CD11a monoclonal antibody (mAb) is administered. We show that recipient pretreatment followed by a brief (13 days) treatment course with high-dose anti-CD11a mAb alone produces long-term survival of cardiac allografts in the rigorous, nonprimarily vascularized heart allograft model in mice. This treatment regimen induces specific unresponsiveness in our model. In recipients bearing long-term beating cardiac grafts after treatment with anti-CD11a mAb, there still exists a high frequency of potentially antigen-reactive T cells in isolated peripheral blood lymphocyte fractions. Therefore, clonal deletion does not appear to explain the induction of specific unresponsiveness by treatment with anti-CD11a mAb in this model. These findings support the further investigation of the use of high-dose anti-LFA-1 mAb monotherapy in the pre- and early postoperative period to promote solid organ allograft survival.
Nakakura
E K
EK
Department of Cardiothoracic Surgery, Stanford University Medical Center, California 94305-5247, USA.
Shorthouse
R A
RA
Zheng
B
B
McCabe
S M
SM
Jardieu
P M
PM
Morris
R E
RE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000917:Antibody Formation; D000939:Epitopes; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1