Mechanisms of lysis by murine cytolytic and helper T cell clones

Although the cytolytic activity of certain T lymphocytes has been recognized for many years, the precise mechanism(s) by which lethal injury occurs has eluded definitive characterization. 1-4 Cytolytic activity has generally been associated with the subset of T cells that recognize antigen (Ag) in the context of class I major histocompatibility complex (MHC) molecules, and that express the CD8 cell surface molecule. In contrast, T cells expressing the CD4 cell surface molecule generally recognize antigen (Ag) in the context of MHC class II molecules, and have been characterized primarily by the particular array of lymphokines (including B cell and/or T cell growth factors) that they produce. Helper T lymphocytes (HTL) type I (TH1) produce interleukin-2 (IL-2) and interferon (IFN) but not IL-4, while HTL type II (TH2) produce IL-4 but not IL-2 or IFN. 5 Exceptions to these functional correlations have been observed. Some CD8⁺ T cells may produce arrays of lymphokines similar to those produced by TH1 cells, 6 , 7 and some CD4⁺ cells (including TH1 cells) have been shown to lyse target cells bearing Ag. 8-10 The lytic activity of TH2 cells is less well characterized; some reports suggest that TH2 cells are unable to lyse Ag-presenting cells (APC) 8 , 11 while other reports indicate that certain TH2 clones can lyse APC. 12-14 Several factors may have contributed to the differences observed in the lytic ability of CD4⁺ T lymphocytes: (1) properties of the APC which serve as target cells as well as properties of the effector T cell can affect the assessment of lytic activity, (2) differences may exist in the lytic mechanisms utilized by certain T cell subsets, and (3) strain differences or Ag-related differences may affect the frequency of cytolytic CD4⁺ T cells that can be detected.