The role of non-adhesive T-cell-accessory cell interactions in the induction of T-cell proliferative hyporesponsiveness

M. A.A. Ibrahim*, B. M. Chain, D. R. Katz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)521-531
Number of pages11
JournalImmunology
Volume81
Issue number4
Publication statusPublished - 1994

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