The role of non-adhesive T-cell-accessory cell interactions in the induction of T-cell proliferative hyporesponsiveness.
We have suggested previously that induction of T-cell proliferative hyporesponsiveness is associated with a defective adhesive T-cell-antigen-presenting cell (APC) interaction. In the previous study, the hyporesponsiveness was allospecific, implying that a T-cell receptor-major histocompatibility complex (MHC) interaction had occurred. Therefore, we hypothesized that this type of non-adhesive T-cell-APC interaction might induce T-cell tolerance rather than activation. This hypothesis has now been tested further in the present study, using two experimental approaches. Firstly, L cells, which express a T-cell receptor ligand, i.e. MHC class II molecules, but lack the capacity to bind to T cells and do not express the crucial receptor/counter receptor lymphocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1 (ICAM-1) pair, also induced non-allospecific T-cell proliferative hyporesponsiveness; this was not due to any direct inhibitory effect on the T cells. Secondly, monoclonal antibodies (mAb) directed to LFA-1 and ICAM-1 were used to disrupt T-cell-APC adhesion specifically, while allowing for T-cell receptor-MHC interaction to occur. The results of this new study suggest that the non-allospecific T-cell proliferative hyporesponsiveness induced was a function of direct T-cell inhibitory effects of these mAb. Taken together, these experiments add further evidence to support the notion that accessory cells which engage T-cell receptors without providing the necessary co-stimulatory signals induce T cells which are in a state of functional 'paralysis' with respect to the antigen which the T-cell receptor recognizes.
Ibrahim
M A
MA
Department of Immunology, University College London Medical School, U.K.
Chain
B M
BM
Katz
D R
DR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1