       Document 0539
 DOCN  M9620539
 TI    CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced
       experimental autoimmune encephalomyelitis and inhibits Th1 but spares
       Th2 cytokines in the central nervous system.
 DT    9602
 AU    Khoury SJ; Akalin E; Chandraker A; Turka LA; Linsley PS; Sayegh MH;
       Hancock WW; Multiple Sclerosis Unit, Brigham and Women's Hospital,
       Harvard; Medical School, Boston, MA 02115, USA.
 SO    J Immunol. 1995 Nov 15;155(10):4521-4. Unique Identifier : AIDSLINE
       MED/96062263
 AB    We studied the contribution of the CD28-B7 costimulatory T cell
       activation pathway to the pathogenesis of experimental autoimmune
       encephalomyelitis in the Lewis rat model. Systemic administration of
       CTLA4Ig suppressed clinical disease and was effective even when CTLA4Ig
       was delayed until day 10 postimmunization, a time when pathologic
       disease is evident. This protection was not reversible by systemic
       administration of high doses of IL-2. Detailed immunohistologic studies
       showed that CTLA4Ig therapy resulted in suppression of the inflammatory
       response with inhibition of Th1 (IL-2 and IFN-gamma) and sparing of Th2
       (IL-4, IL-10, and IL-13) cytokines in the central nervous system. These
       results indicate that the CD28-B7 T cell costimulatory pathway plays an
       important role in experimental autoimmune encephalomyelitis, a
       Th1-mediated disease, and suggest that blockade of this costimulatory
       pathway protects against active disease by causing a state of immune
       deviation towards Th2 function. The ability of CTLA4Ig to treat animals
       with pathologically established disease may have important clinical
       implications for patients with multiple sclerosis.
 DE    Animal  Antigens, CD28/*METABOLISM  Antigens,
       Differentiation/*PHARMACOLOGY  Central Nervous System/IMMUNOLOGY
       Cytokines/METABOLISM  Encephalomyelitis, Allergic/IMMUNOLOGY/*PREVENTION
       & CONTROL  Interleukin-2/PHARMACOLOGY  Lymphocyte Transformation/DRUG
       EFFECTS  Rats  Rats, Inbred Lew  Signal Transduction  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Th1 Cells/*IMMUNOLOGY  Th2
       Cells/*IMMUNOLOGY  JOURNAL ARTICLE

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

