+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Antibodies to adhesion molecules inhibit the lytic function of MHC-unrestricted cytotoxic cells by preventing their activation

Antibodies to adhesion molecules inhibit the lytic function of MHC-unrestricted cytotoxic cells by preventing their activation

Cellular Immunology. 143(2): 389-404

We evaluated the effect of the antibodies to adhesion molecules CD2, CD11a/CD18 (LFA-1), and CD56 (N-CAM) on MHC-unrestricted cytotoxicity mediated by polyclonal NK cells and LAK cells or by CD3+ or CD3- cytolytic cells clones against a panel of tumor cell targets selected according to expression or absence of the corresponding ligands. We show that (i) antibodies to CD11a/CD18 and, to a lesser extent, antibodies to CD2 inhibit target cell lysis, whereas anti-CD56 antibodies exert little if any effect; (ii) in a model system using polyclonal NK/LAK cells as effectors and K562 or HL60-R (NK-resistant) cells as targets, inhibition of cytotoxicity occurs without a significant impairment of effector to target cell binding; (iii) the cytotoxic function of CD3+ or CD3- cytotoxic cells clones is inhibited differentially by antibodies to adhesion molecules; (iv) conjugates formed in the presence of antibodies which inhibit target cell lysis display a significant reduction of target to effector cell contact surface; and (v) this may lead to defective activation of effector cells, as indicated by lack of redistribution of the microtubular apparatus. We conclude that (i) MHC-unrestricted cytotoxicity is regulated by a number of molecular interactions that span far beyond our present knowledge nad that it is strictly dependent on the surface phenotype of the effector cell and of the target cells; (ii) in certain types of effector/target cell interactions, antibodies to adhesion molecules do not prevent conjugate formation but reduce the extent of cell-to-cell surface contact which, in turn, leads to defective activation of the effector cell and, therefore, to inhibition of target cell lysis.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 008169908

Download citation: RISBibTeXText

PMID: 1380897

DOI: 10.1016/0008-8749(92)90035-n

Related references

Salicylates inhibit adhesion and transmigration of T lymphocytes by preventing integrin activation induced by contact with endothelial cells. Blood 92(7): 2389-2398, 1998

Monoclonal antibodies specific for H-2K and H-2D antigens on cytotoxic T cells can inhibit their function. Proceedings of the National Academy of Sciences of the United States of America 83(5): 1443-1447, 1986

Anti-leucocyte function-associated antigen-1 antibodies inhibit T-cell activation following low-avidity and adhesion-independent interactions. Immunology 79(4): 548-555, 1993

Function of adhesion molecules lymphocyte function-associated antigen-3 and intercellular adhesion molecule-1 on human epidermal Langerhans cells in antigen-specific T cell activation. Journal of Immunology 152(7): 3400-3409, 1994

Monoclonal antibodies against adhesion molecules can inhibit plasma cell induced interleukin 6 production by bone marrow stromal cells. British Journal of Haematology 87(Suppl. 1): 224, 1994

Antibodies against animal substrate adhesion molecules inhibit adhesion of Phytophthora megasperma f sp glycinea to the host cell wall. Phytopathology 82(10): 1118, 1992

Characterization of factors regulating successful immunotherapy using a tumor-specific cytotoxic T lymphocyte clone: Role of interleukin-2, cycling pattern of lytic activity and adhesion molecules. International Journal of Cancer 60(6): 828-836, 1995

Functions of adhesion molecules during cerebellar cortex formation differential effects on granule cell migration by antibodies to neural cell adhesion molecules neuron glia adhesion molecules and cytotactin. Society For Neuroscience Abstracts: 318, 1986

B7 costimulation is necessary for the activation of the lytic function in cytotoxic T lymphocyte precursors. Journal of Immunology 155(11): 5167-5174, 1995

Antibodies against cell adhesion molecules inhibit proliferation of uveitogenic lymphocytes in vitro. Nussenblatt, R B, Whitcup, S M, Caspi, R R, Gery, I International Congress Series; Advances in ocular immunology 39-42, 1994

Recombinant glycoproteins that inhibit complement activation and also bind the selectin adhesion molecules. Journal of Biological Chemistry 274(16): 11237-11244, 1999

Novel non-peptide small molecules preventing IKKβ/NEMO association inhibit NF-κB activation in LPS-stimulated J774 macrophages. Biochemical Pharmacology 104: 83-94, 2016

Complement receptors (CR) and cytotoxic responses: monoclonal antibodies directed against CR1 and CR3 inhibit the generation of human allospecific and virus specific cytotoxic cells in vitro. Journal of Immunopharmacology 8(1): 75-88, 1986

Statins inhibit ox-LDL-induced expression of adhesion molecules and monocyte adhesion to human coronary endothelial cells Role of mitogen-activated protein kinase and NF-kappaB. Circulation 102(18 Suppl.): II 251, 2000

Anti-CD3-activated killer T cells: Interleukin-6 modulates the induction of major histocompatibility complex-unrestricted cytotoxicity and the expression of genes coding for cytotoxic effector molecules. Journal of Interferon and Cytokine Research 17(12): 727-737, 1997