Document 0093
 DOCN  M9580093
 TI    Synergistic effects of IL-7 and IL-12 on human T cell activation.
 DT    9506
 AU    Mehrotra PT; Grant AJ; Siegel JP; Laboratory of Cellular Immunology,
       Food and Drug Administration,; Rockville, MD 20852, USA.
 SO    J Immunol. 1995 May 15;154(10):5093-102. Unique Identifier : AIDSLINE
       MED/95248073
 AB    We have previously demonstrated that human rIL-12 alone can augment the
       development of cytotoxic activity in stimulated CD8+ T cells. The
       present study was undertaken to examine the interactions of rIL-7 and
       rIL-12 on human peripheral blood T cell activation and CTL
       differentiation. Purified T lymphocytes were pulsed overnight with
       immobilized alpha-CD3 and then cultured for 3 additional days with IL-7
       and/or IL-12. The combination of IL-7 and IL-12 synergistically enhanced
       the proliferation of either fresh CD3+ T cells or an IL-2-dependent CD4+
       T cell line, Kit-225-K6. This synergy was seen on both subsets of T
       cells; however, CD8+ T cells were usually more responsive to IL-7 and
       IL-12 at lower concentrations than were CD4+ T cells. Furthermore, these
       cytokines additively/synergistically augmented the cytotoxic activity of
       CD8+ T cells. Abs to IL-2 and IL-2R alpha blocked the synergistic effect
       on proliferation of CD4+ T cells, but had a minimal effect on the
       synergistic response of the proliferative and cytotoxic activity of CD8+
       T cells. Examination of the effects of IL-7 and IL-12 on the expression
       of IL-12 receptor on T cells revealed an increase in the subunit of
       IL-12R by IL-7 as determined by flow cytometric analysis. We analyzed
       the effects on IFN-gamma production by CD8+ T cells and found that IL-7
       alone did not induce detectable levels of IFN-gamma production but
       together with IL-12 it synergistically enhanced the production of
       IFN-gamma. We also found that IFN-gamma was probably not required for
       enhanced CTL activity of CD8+ T cells, because Ab to human IFN-gamma did
       not block additive/synergistic effects of either cytokine. The
       synergistic stimulatory activity of IL-7 and IL-12 may be of
       significance in vivo and may provide an alternative mechanism of
       stimulating T cells for use in immunotherapy.
 DE    Antibodies, Monoclonal/IMMUNOLOGY  Cells, Cultured  Cytotoxicity Tests,
       Immunologic  Cytotoxicity, Immunologic/DRUG EFFECTS  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/DRUG
       EFFECTS/IMMUNOLOGY  Drug Synergism  Enzyme-Linked Immunosorbent Assay
       Flow Cytometry  Human  Interferon Type II/BIOSYNTHESIS
       Interleukin-12/IMMUNOLOGY/*PHARMACOLOGY  Interleukin-2/PHYSIOLOGY
       Interleukin-7/IMMUNOLOGY/*PHARMACOLOGY  Lymphocyte Transformation/*DRUG
       EFFECTS/IMMUNOLOGY  Receptors, Interleukin/BIOSYNTHESIS  Recombinant
       Proteins/PHARMACOLOGY  T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY
       Up-Regulation (Physiology)/PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).