T Lymphocyte-Mediated Cytolysis — A Comprehensive Theory I. The Mechanism of CTL-Mediated Cytolysis
The mechanism(s) by which cytotoxic T lymphocyte (CTL) cause lethal and irreversible damage to target cells (TC) has been the subject of considerable research during the past 10–15 years. A number of mechanisms have been proposed, examined, and either have been disproved or have generally not been pursued for lack of convincing experimental evidence in their support. These have included involvement of CTL-associated complement-like components (1,2); direct transfer of molecules, from the CTL to the TC membrane or cytoplasm, that eventually result in death of the target cell (3,4); localized extracellular secretion by the CTL, upon specific contact with the TC, of cytotoxic molecules (5,6); tangential shearing of the TC membrane as a result of CTL-TC conjugation (7); distortion of TC membrane potential (8); and Implication of the CTL membrane as a generalized cytotoxic agent (9). These and other proposed mechanisms have been extensively reviewed (see ref. 10–13). Despite a great deal of imaginative experimentation in pursuit of these various hypotheses, none of them has attracted widespread support as a principle mechanism of CTL-mediated cytolysis.
KeywordsConformational Distortion Annular Lipid Lytic Mechanism Target Cell Binding Mediate Cytolysis
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