Regulation of lymphocyte aggregation and proliferation through adhesion molecule CD54 (ICAM-1).
The effect of two mouse mAb (LB-2 and G1B2) against human CD54 (intercellular adhesion molecule-1, ICAM-1) in lymphocyte aggregation and proliferation systems was investigated. The LB-2 mAb, but not G1B2, inhibited phorbol ester-induced aggregation of B lymphoblastoid cells. In addition, LB-2, but not G1B2, induced aggregation and proliferation of peripheral blood mononuclear cells (PBMC) in cultures containing FCS. The Fab fragment of LB-2 always (10/10 donors) induced proliferation while the intact mAb was active in 3/11 donors. When cultures contained human serum (HS), LB-2 and its Fab fragment induced proliferation in 1/9 and 1/4 donors, respectively. Addition of HS to FCS cultures inhibited proliferation induced by LB-2 Fab, indicating the presence of an inhibitory factor in human serum. Addition of anti-CD18 mAb to cultures stimulated by LB-2 Fab caused partial inhibition of proliferation but did not prevent aggregate formation. A combination of anti-CD18 and anti-CD29 mAb resulted in a nearly complete inhibition of proliferation but did not inhibit aggregate formation. In these experiments it was found that the anti-CD29 mAb 4B4 in itself induced cell aggregation of PBMC and enhanced aggregation induced by the anti-CD3 mAb OKT3. Both LB-2 and G1B2 showed significant inhibition (> 60%) of proliferation when human PBMC were stimulated by the antigen PPD in the presence of HS, but not when stimulated by staphylococcal enterotoxin A (SEA) or IL-2. This study describes two mAb against separate epitopes on CD54 which are differentially involved in cell aggregation or induction of proliferation but are of similar importance in antigen-specific responses. Furthermore, the new finding that the LB-2 mAb or its Fab fragment can induce cell aggregation and proliferation defines a signaling function of CD54 which may work independent of crosslinking or costimulation.
Grönberg
A
A
Kabi Pharmacia AB, Uppsala, Sweden.
Halapi
E
E
Ferm
M
M
Petersson
M
M
Patarroyo
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1