CD4+ T lymphocyte-induced target cell detachment. A model for T cell-mediated lytic and nonlytic inflammatory processes.
We have been exploring the hypothesis that T lymphocytes have the potential to mediate immune damage through nonlytic disruption of tissue organization. In this report, we have examined the ability of purified, primary cultures of alloreactive CD4+ T cells to mediate Ag-specific target cell detachment and/or lysis of L cell lines transfected with MHC class II determinants. Using this model, we demonstrate that: 1) MHC class II-specific CD4+ T cells can cause detachment as a distinct event of the E:T interaction, although the pathways or mechanisms involved appear to be different from those utilized by MHC class I-specific CD8+ T cells; 2) detachment and lysis by CD4+ T cells are distinct activities that involve different functional requirements: 3) CD4+ T cell-induced detachment is initiated by direct cell-cell interaction, independent of TNF-alpha/beta; 4) CD4+ T cell-mediated lysis can be accomplished by TNF-alpha/beta-dependent and independent pathways; and 5) the nature of a particular target cell response to alloreactive CD4+ T cell attack reflects its intrinsic susceptibility to one or more potential effector mechanisms.
Abrams
S I
SI
Department of Pharmacology, Washington University School of Medicine, St Louis, MO 63110.
Russell
J H
JH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D007739:L Cells; D008233:Lymphotoxin-alpha / Q000502:physiology; D014176:Protein Biosynthesis; D011994:Recombinant Proteins; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha