Intercellular adhesion molecule-1/leukocyte function associated antigen-1 blockade inhibits alloantigen specific human T cell effector functions without inducing anergy.
BACKGROUND
Intercellular adhesion molecule (ICAM-1) is important in leukocyte adhesion-dependent events and some data suggest that ICAM-1 provides T cell costimulation. We anlayzed the role of the ICAM-1 and leukocyte function associated antigen-1 (LFA-1) interaction in human T cell alloreactivity in vitro.


METHODS
Allo-antigen-induced T cell proliferation and cytotoxic T lymphocyte lytic activity were assessed by mixed lymphocyte reaction assay and 51 Chromium release assay, respectively. Immunostaining and flow cytometry were used to assess the expression of receptors on activated T cells.


RESULTS
Alloantigen-induced T cell proliferation and cytotoxic T lymphocyte activity were markedly inhibited by antibodies to ICAM-1 and LFA-1. These antibodies had to be present at the time of initial T cell receptor/antigen engagement to inhibit proliferation. Neither IL-2 nor IL-4 were involved in the observed inhibition by antibodies. Inhibition was not associated with altered cell surface expression of receptors such as CD3, CD4, ICAM-1, LFA-1, CD25, and HLA-DR however, these antibodies did impede the ability of generation of functionally active T cells. Interestingly, these antibodies inhibited soluble, but not immobilized OKT3-induced proliferation of peripheral blood leukocytes. Antibody-mediated inhibition of proliferation failed to impair the ability of T cells to subsequently proliferate in response to stimulation by the original or third party alloantigen or mobilize [Ca++]i in response to CD3 or LFA-1 receptor ligation.


CONCLUSIONS
These data demonstrate that blockade of ICAM-1/LFA-1 binding at the time of allorecognition potently blocks initial T cell effector functions that could be due to lack of effective T cell/APC engagement.
Calhoun
R F
RF
Department of Surgery, Washington University School of Medicine St. Louis, Missouri 63110, USA.
Oppat
W F
WF
Duffy
B
B
Mohanakumar
T
T
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D020013:Calcium Signaling / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D000939:Epitopes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D016853:Muromonab-CD3 / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D000906:Antibodies; D000939:Epitopes; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D016853:Muromonab-CD3; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1