       Document 0824
 DOCN  M9590824
 TI    Inhibition of T cell responses by activated human CD8+ T cells is
       mediated by interferon-gamma and is defective in chronic progressive
       multiple sclerosis.
 DT    9509
 AU    Balashov KE; Khoury SJ; Hafler DA; Weiner HL; Center for Neurologic
       Diseases, Brigham and Women's Hospital,; Harvard Medical School, Boston,
       Massachusetts 02115, USA.
 SO    J Clin Invest. 1995 Jun;95(6):2711-9. Unique Identifier : AIDSLINE
       MED/95286835
 AB    The autologous mixed lymphocyte reaction (AMLR) involves the activation
       of T cells by autologous antigen presenting cells. Cells are generated
       during the course of the AMLR that have suppressive properties in vitro.
       In the present study we investigated the induction of CD8+ T cells in
       the AMLR with suppressive properties and the mechanism by which these
       cells downregulate in vitro proliferative responses. Purified CD8+ but
       not CD4+ T cells activated in the AMLR in conditioned medium inhibited
       proliferation of autologous T cells by anti-CD3 or PPD. Nonactivated
       CD8+ T cells did not suppress. The CD8+ T cells activated in the AMLR in
       the presence of conditioned medium (CD8+ Tact) were CD11b negative and
       were noncytotoxic. The inhibitory effect of CD8+ Tact cells was
       completely abrogated by anti-IFN-gamma antibody, but not by anti-IL-4,
       anti-IL-10, or anti-TGF-beta antibody. The induction of CD8+ Tact cells
       in the AMLR was blocked by anti-IL-2 or by anti-GM-CSF antibody and the
       combination of these two recombinant cytokines could support the
       induction of suppressive CD8+ Tact cells. CD8+ Tact cells were defective
       in patients with chronic progressive multiple sclerosis (MS) as compared
       to patients with relapsing-remitting MS or normal controls. Our studies
       provide a basis for understanding the mechanism of suppression by human
       CD8+ T cells in terms of specific cytokines, and demonstrate the
       potential importance of these cells in a human autoimmune disease as
       their function is defective in patients with progressive MS.
 DE    CD8-Positive T-Lymphocytes/*IMMUNOLOGY  Granulocyte-Macrophage
       Colony-Stimulating Factor/PHARMACOLOGY  Human  Immune Tolerance  In
       Vitro  Interferon Type II/*PHYSIOLOGY  Interleukin-2/PHARMACOLOGY
       Lymphocyte Culture Test, Mixed  Lymphocyte Transformation  Multiple
       Sclerosis/*IMMUNOLOGY  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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

