Question

There are a number of drugs in clinical development that bind to LFA-1 and modulate its interaction with ICAM-1. These drugs do not prevent the binding of LFA-1 to ICAM, but rather increase the dissociation rate of LFA-1 from ICAM-1 (i.e. make LFA-1 fall off of ICAM-1 faster). What effect would such a drug have on T-cell function? Speculate for what conditions/pathologies this drug might be beneficial. Explain

Answer 1

#. LFA-1 antagonists affect cell cluster formation in response to mitogenic stimulation as well as DC-induced T-cell proliferation. To this end, CD4+ T cells were activated with the mitogenic agent PHA, which is known to induce LFA-1-mediated homotypic cell-to-cell adhesion.

#. It is used to treat Dry eye disease ( keratoconjunctivitis )

Intercellular adhesion molecule-1 (ICAM-1) may be overexpressed in corneal and conjunctival tissues in dry eye disease. The integrin lymphocyte function-associated antigen-1 (LFA-1) interacts with ICAM-1 to contribute to the formation of an immunological synapse, resulting in T-cell activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines in human peripheral blood mononuclear cells.