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-α/β; 4) CD4⁺ T cell-mediated lysis can be accomplished by TNF-α/β-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.