Molecular Events in Late Stages of T-Cell Functional Maturation

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Abstract
Peripheral blood lymphocytes activated with either the calcium ionophore A23187 or the combination of anti-CD2 monoclonal antibodies, 9.6 + VIT13, undergo blast formation and proliferation but do not develop cytolytic activity. These proliferating blasts, referred to as pre-effector blasts because they do not yet express cytolytic function, respond to stimulation with interleukin-2 (IL-2) by further proliferation and development of cytolytic activity, i.e. they become effector cells. Pre-effector blasts activated with 9.6 + VIT13, but not A23187-activated pre-effector blasts, also respond to stimulation with interferon-gamma (IFN-gamma) by becoming cytolytic effector cells. This report examines gene expression (by Northern blot analysis) in pre-effector blasts and during the transition from the pre-effector to the effector stage. The data presented here provide further support for the concept that A23187 activation drives T cells to become dividing blasts that are appropriately referred to as 'pre-effector' cells in that these blasts do not express transcripts for granzyme A or perforin mRNA but are driven by IL-2 to do so in parallel with the acquisition of cytotoxic function. Cells are apparently driven by 9.6 + VIT13 to a later stage of functional maturation than by A23187 activation; 9.6 + VIT13-activated pre-effector blasts express mRNA for both granzyme A and perforin, even though these blasts do not express cytolytic activity. Activation via A23187 results in lower expression of the proto-oncogene c-myb relative to that found in either 9.6 + VIT13 or OKT3-activated cells.