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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).