title: Differential dependence of TH-0, TH-1 and TH-2 CD4+ T cells on co-stimulatory activity provided by the accessory molecule LFA-1.
abstract: 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/CD18) 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 CD11a 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 CD11a and CD18 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 (HA1-7; TH-0). In contrast, soluble antibodies to CD18 inhibited proliferative responses of both DE-9 and HA1.7 to an immunogenic challenge of antigen and to stimulation by anti-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, St Mary's Hospital Medical School, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Faith
authors.forename: J A
authors.initials: JA
authors.lastname: Higgins
authors.forename: R E
authors.initials: RE
authors.lastname: O'Hehir
authors.forename: J R
authors.initials: JR
authors.lastname: Lamb
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002999:Clone Cells; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1