Molecular events in late stages of T-cell functional maturation.
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.
Nelson
P J
PJ
Department of Laboratory Medicine/Pathology and Surgery, University of Minnesota, Minneapolis.
Geller
R L
RL
Podack
E
E
Bach
F H
FH
D015152:Blotting, Northern; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D053804:Granzymes; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
D006681:HLA-D Antigens; D007376:Interleukin-2; C000715470:MAS1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human