Document 0796 DOCN M95A0796 TI Requirements for activation of CD8+ murine T cells. I. Development of cytolytic activity. DT 9510 AU Cronin DC 2nd; Lancki DW; Fitch FW; Department of Pathology, University of Chicago, IL 60637, USA. SO Immunol Res. 1994;13(4):215-33. Unique Identifier : AIDSLINE MED/95341106 AB Cytolytic effector function fails to develop if proliferation of allospecific cytolytic T lymphocyte precursors is inhibited, but the requirements for generation of cytolytic activity have not been fully defined. In contrast, the cytolytic effector function of cytolytic T lymphocyte clones does not change during the cell cycle, and the level of cytolytic activity is independent of cellular proliferation. The requirement for proliferation by primary responding populations may reflect the need for clonal expansion of a few inherently cytolytic effector cells in order to reach a threshold number which can readily be detected in conventional cytolytic assays. Alternatively, proliferation may be required for cytolytic T lymphocyte precursors to differentiate into mature, functional cytolytic cells. Using CD8+ T cells which express an antigen-specific transgenic alpha/beta T cell receptor, we have studied the requirements for acquisition of cytolytic capacity. Stimulation of the T cell receptor alone appears to be sufficient to render naive, CD8+ transgenic T cells sensitive to the growth effects of interleukin-2 (IL-2), and in some circumstances to interleukin-4 (IL-4), but not to induce either lymphokine production or cytolytic activity. Costimulatory molecules expressed by allogenic stimulating cells appear to be required for lymphokine production, and CD8+ transgenic T cells initially appear to secrete only IL-2 and interferon-gamma. Stimulation of the T cell receptor of naive, CD8+ transgenic T cells appears to induce cytolytic activity only if cell proliferation occurs, either in response to IL-2 produced by the stimulated cells themselves when costimulatory molecules are present, or to IL-2 or IL-4 from exogenous sources if costimulatory molecules are absent. DE Animal Antibodies, Monoclonal/PHARMACOLOGY Antigens, CD8/DRUG EFFECTS/IMMUNOLOGY Aphidicolin/PHARMACOLOGY Cell Cycle Cells, Cultured Cytotoxicity, Immunologic CD8-Positive T-Lymphocytes/DRUG EFFECTS/*IMMUNOLOGY Female Hydroxyurea/PHARMACOLOGY Interferon Type II/SECRETION Interleukin-2/PHARMACOLOGY/SECRETION Interleukin-4/PHARMACOLOGY *Lymphocyte Transformation/DRUG EFFECTS Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Mimosine/PHARMACOLOGY Receptors, Antigen, T-Cell/DRUG EFFECTS/IMMUNOLOGY Receptors, Antigen, T-Cell, alpha-beta/DRUG EFFECTS/IMMUNOLOGY Recombinant Proteins/PHARMACOLOGY Serine Proteinases/ANALYSIS Spleen/ENZYMOLOGY/IMMUNOLOGY Support, U.S. Gov't, P.H.S. T-Lymphocytes, Cytotoxic/DRUG EFFECTS/IMMUNOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).