T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA‐1‐mediated events

Jonathan M. Green, Xiang‐Guang ‐G Zheng, Yoji Shimizu, Craig B. Thompson, Laurence A. Turka

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge. In this manuscript we specifically examine the role of two accessory molecules, CD28 and LFA‐1, in modulating the T cell proliferative response to a variety of stimuli. We demonstrate that the proliferation induced by staphylococcal enterotoxins A and B in combination with CD28 costimulation is dependent on LFA‐1‐mediated events. This requirement for LFA‐1 is independent of T cell‐accessory cell adhesion. Similarly, an allogeneic mixed lymphocyte reaction, which has previously been shown to be a CD28‐dependent response, can be inhibited by blockade of LFA‐1. This suggests LFA‐1 plays an essential role in these responses, either by enhancing intercellular adhesion or by an independent signal transduction event. In contrast, when the primary activating stimulus is delivered by immobilized anti‐CD3 antibody or by PMA, and the secondary stimulus by either α‐CD28 or cell‐bound CD28 ligand B7, there is no requirement for LFA‐1. In addition, we demonstrate that cross‐linking of LFA‐1 with immobilized monoclonal antibody, or engagement of LFA‐1 with ICAM‐1 expressed on the surface of a CHO cell, provide an insufficient costimulus for T cell proliferation initiated by enterotoxin, immobilized α‐CD3 or phorbol ester. Our data suggests that LFA‐1, in contrast to CD28, functions not as a costimulatory molecule, but serves primarily to modulate the signal delivered through the T cell receptor.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalEuropean Journal of Immunology
Volume24
Issue number1
DOIs
StatePublished - Jan 1994

Keywords

  • CD28
  • Costimulation
  • LFA‐1
  • Superantigen
  • T cell activation

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