Functional antibodies to leukocyte adhesion molecules in antithymocyte globulins.
BACKGROUND
Polyclonal antithymocyte globulins (ATG) induce T-cell depletion and functional impairment of nondeleted lymphocytes. Interference of ATG with the main leukocyte surface molecules involved in cellular adhesion and leukocyte-endothelium interaction was investigated in the present study.


METHODS
In three rabbit ATG, the authors measured antibodies to integrins, beta2-integrin ligands, and chemokine receptors by flow cytometry; chemotactic responses; and down-modulation of cell surface expression on lymphocytes, monocytes, and neutrophils.


RESULTS
Antibodies to CD11a/CD18 (leukocyte function-associated antigen-1 [LFA-1]) present in ATG induced a dose-dependent down-modulation of cell surface expression of this beta2 integrin on lymphocytes, monocytes, and neutrophils. In contrast, anti-LFA-1 monoclonal antibodies did not induce LFA-1 modulation unless cross-linked by a second antibody. ATG also contained functional antibodies to the beta1 integrin CD49d/CD29 (VLA-4), the alpha4beta7 integrin, CD50, CD54, and CD102 but not to CD62L. ATG were shown to bind to CXCR4 and CCR7 on lymphocytes, CXCR4, and CCR5 on monocytes; to down-modulate cell surface expression of CCR7; and to decrease monocyte chemotactic response to CCL5 (RANTES) and lymphocyte chemotactic response to CCL19 (MIP-3beta).


CONCLUSIONS
These results show that ATG may interfere with leukocyte responses to chemotactic signals but mostly inhibit the expression of integrins required for firm cellular adhesion. The latter property of inhibition is not shared by monoclonal antibodies, and it may contribute to decreasing graft cellular infiltration during acute rejection and possibly after postischemic reperfusion.
Michallet
Marie-Cécile
MC
Immunopharmacology unit, INSERM, Lyon, France.
Preville
Xavier
X
Flacher
Monique
M
Fournel
Sylvie
S
Genestier
Laurent
L
Revillard
Jean-Pierre
JP
D000818:Animals; D000906:Antibodies / Q000032:analysis* / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology; D000961:Antilymphocyte Serum / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D019707:Receptors, Chemokine / Q000276:immunology; D019087:Selectins / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000961:Antilymphocyte Serum; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D019707:Receptors, Chemokine; D019087:Selectins; D018799:Intercellular Adhesion Molecule-1