title: Both LFA-1-positive and -deficient T cell clones require the CD2/LFA-3 interaction for specific cytolytic activation.
abstract: We investigated the capacity of T lymphocytes from a leukocyte adhesion-deficient (LAD) patient to respond to alloantigen. Leukocytes of this patient completely lacked LFA-1 surface expression due to the absence of mRNA coding for the LFA-1 beta chain. Despite the absence of LFA-1, T lymphocytes obtained from this patient, cultured with allogeneic stimulator cells (lymphoblastoid B cells JY), were capable of lysing JY cells. Furthermore, two T cell clones (one CD4+ and one CD8+), generated from this lymphocyte culture, specifically lysed the allogeneic lymphoblastoid JY cells. The cytolytic capacity of LFA-1-negative T lymphocytes and T cell clones was comparable to that of control LFA-1-positive T cells with allospecificity against JY. Detailed analysis of the CD4 positive and LFA-1-negative T cell clone demonstrated that it specifically recognized HLA-DQ. Antibody inhibition studies showed that the CTL/target cell interaction was mediated through the CD2/LFA-3 adhesion pathway. LFA-1 expressed by the target cells did not participate in the CTL/target cell conjugate formation and contributed only minimally to the cytotoxic activity. Moreover, when allogeneic LFA-1-deficient B cells, bearing the appropriate HLA-DQ alloantigen, were used as target cells, significant levels of specific cytotoxicity were measured, further excluding a role for LFA-1 in this interaction. The adhesion molecules, VLA-4, CD44 and L-selectin (LECAM1) were not involved. These results demonstrate that LFA-1-negative T lymphocytes can exert allospecific cytotoxicity and that CTL/target cell contact is mediated through the CD2/LFA-3 route. This observation may explain in part why in LAD patients viral infections, cleared largely by T cells, are less frequently observed than bacterial infections, in which phagocytic cells play a major role.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
authors.forename: E
authors.initials: E
authors.lastname: Van de Wiel-van Kemenade
authors.forename: A A
authors.initials: AA
authors.lastname: Te Velde
authors.forename: A J
authors.initials: AJ
authors.lastname: De Boer
authors.forename: R S
authors.initials: RS
authors.lastname: Weening
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: J
authors.initials: J
authors.lastname: Borst
authors.forename: C J
authors.initials: CJ
authors.lastname: Melief
authors.forename: C G
authors.initials: CG
authors.lastname: Figdor
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D015152:Blotting, Northern; D018801:CD2 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018968:CD58 Antigens; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules; D002455:Cell Division; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D053804:Granzymes; D006683:HLA-DQ Antigens / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D012313:RNA / Q000032:analysis; D011971:Receptors, Immunologic / Q000502:physiology*; D012697:Serine Endopeptidases / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D006683:HLA-DQ Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1; D012313:RNA; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human