Regulation of T lymphocyte subsets

Patterns of cytokine secretion and functional differences distinguish T lymphocyte subsets, T lymphocyte subsets are also regulated differentially. Most established CD8(+) lymphocyte clones secrete gamma-interferon (IFN-gamma) but not interleukin 2 (IL-2) or IL-4. Using murine T cells which express a transgenic, antigen-specific alpha/beta T cell receptor (TCR) specific for L(d) class I major histocompatibility complex antigen, we have found that CD8(+) lymphocytes can be divided into functional subsets. Freshly isolated CD8(+) T cells are not cytolytic, do not proliferate and do not secrete cytokines, Stimulation of TCR alone does not induce cytokine secretion, but cells become responsive to exogenous IL-2 or IL-4. Stimulation of CD28 together with TCR induces secretion of IL-2 and IFN-gamma, and cells proliferate without exogenous cytokines. Proliferation is necessary for the development of cytolytic activity. If IL-4 is present during initial stimulation. IL-4 is secreted following restimulation. Upon stimulation. some IL-4-producing murine CD8(+) T cell clones express CD40 ligand (CD40L), and they potentiate proliferation and immunoglobulin secretion by small resting B cells. Thus, the CD8(+) T cell subsets T cytotoxic I (Tc1) and Tc2 are analogous to CD4(+) T helper 1 (Th1) and Th2. IL-2 production by naive CD8(+) cells requires co-stimulation. IL-4 production by CD8(+) T cells requires the presence of IL-4 during initial stimulation. Some IL-4-producing CD8(+) T cells express CD40L following TCR stimulation and provide help for B cells.