       Document 0722
 DOCN  M9620722
 TI    Direct inhibition of human CD8+ lymphocyte activation by cyclosporine A
       and Rapamune-Sirolimus.
 DT    9602
 AU    Combates NJ; Degiannis D; Raskova J; Raska K Jr; Johnson and Johnson
       CPWW, Skillman, New Jersey 08558, USA.
 SO    Clin Immunol Immunopathol. 1995 Dec;77(3):221-8. Unique Identifier :
       AIDSLINE MED/96080349
 AB    Cyclosporin A (CsA) and Rapamune-Sirolimus (RAP) have been shown to
       inhibit the in vitro activation of heterogeneous lymphocytes
       populations, but little is known about their direct actions on isolated
       CD8+ lymphocytes. In this study the direct effects of RAP and CsA on a
       highly purified population of CD8+ lymphocytes were examined. Human CD8+
       lymphocytes were purified to near homogeneity and stimulated with
       anti-CD3 antibody, OKT3, or allogeneic cells in the presence of
       exogenous human recombinant interleukin 2 (IL2). The effects of CsA and
       RAP on cell proliferation, the entry into the S phase of the cell cycle,
       the surface expression of Tac antigen, and the release of soluble IL2
       receptor and soluble CD8 were analyzed. When CsA and RAP were included
       in the stimulated CD8+ lymphocyte cultures, these responses were
       inhibited. OKT3-stimulated CD8+ lymphocytes were sensitive to lower
       concentrations of the immunosuppressants than those previously reported
       for peripheral blood mononuclear cells. RAP was effective at a lower
       dose than CsA and when the agents were applied in combination, cell
       proliferation was synergistically inhibited. These results demonstrate
       that CsA and RAP can inhibit the activation and proliferation of
       purified CD8+ lymphocytes in response to OKT3 or alloantigen in the
       presence of IL2.
 DE    Cell Cycle/DRUG EFFECTS  Cells, Cultured  Cyclosporine/*PHARMACOLOGY
       CD8-Positive T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY  Drug Synergism
       Flow Cytometry  Human  Immunosuppressive Agents/*PHARMACOLOGY
       Lymphocyte Culture Test, Mixed  Lymphocyte Transformation/*DRUG EFFECTS
       Muromonab-CD3/IMMUNOLOGY  Polyenes/*PHARMACOLOGY  Receptors,
       Interleukin-2/BIOSYNTHESIS  JOURNAL ARTICLE

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

