Clinical & Experimental Allergy

Differential dependence of TH-0, TH-1 and TH-2 CD4 4+ T cells on co-stimulatory activity provided by the accessory molecule LFA-1

Authors

  • A. FAITH,

    Corresponding author
    1. Departmental of Immunology, St Mary'a Hospital Medical School, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 IPG
      Dr A. Faith, SIAF, Obere Strasse 23. Davos. Switzerland.
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  • J. A. HIGGINS,

    1. Departmental of Immunology, St Mary'a Hospital Medical School, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 IPG
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  • R. E. O'HEHIR,

    1. Departmental of Immunology, St Mary'a Hospital Medical School, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 IPG
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  • J. R. LAMB

    1. Departmental of Immunology, St Mary'a Hospital Medical School, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 IPG
    2. Department of Biology, Imperial College’of Science, Technology and Medicine, London, UK
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Dr A. Faith, SIAF, Obere Strasse 23. Davos. Switzerland.

Summary

Background The adhesion molecule LFA-1 contributes to the activation response of peripheral blood human CD4+ T cells. Less is known of its contribution to stimulation of long-term CD4+ T cell lines and clones or of its potential to co-stimulate CD4+ T cells of different functional phenotype.

Objective This study was therefore performed to investigate co-stimulatory properties of the LFA-1 (CD11a/CD 18) complex in the activation of human CD4+ T cell lines and clones of TH-0. TH-1 and TH-2 subsets.

Methods Co-stimulatory activity was measured by cross-linking antibodies to CD 11a or CD18 with anti-CD3 antibodies to plastic and then measuring the proliferative response of CD4+ T cells to these antibodies.

Results A house duct mite allergen-specific CD4+ T cell line (TH-2) demonstrated much greater dependence on both C'DI la and CD IK than a mycobacterial antigen-specific CD4+ T cell line (TH-1). Co-stimulatory activity through LFA-1 was also provided to a house dust mite-specific CD4+ T cell clone (DE-9; TH-2) but not to an influenza haemagglutinin-specific CD4+ T cell clone (HA 1.7: TH-0). In contrast, soluble antibodies to CD 18 inhibited proliferativc responses of both DE-9 and HA1.7 to an immunogenic challenge of antigen and to stimulation by unti-CD3 antibodies. However, the allergen-specific T cells were more susceptible to inhibition. Signal transduction was also observed from the T-cell receptor to LFA-1. Ligation of the T-cell receptor modulated the phenotypic expression of LFA-1 and ICAM-1 on both HA1-7 and DE-9). Phenotypic modulation was observed as a result of both activation and the induction of non-responsiveness.

Conclusion These experiments indicate that CD4+ T cells of TH-2 functional phenotype may have a greater requirement for the co-stimulatory activity of LFA-1 than CD4+ T cells of TH-0 or TH-1 phenotypes.

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