       Document 0702
 DOCN  M9630702
 TI    Exacerbated autoimmunity associated with a T helper-1 cytokine profile
       shift in H-2E-transgenic mice.
 DT    9603
 AU    Takacs K; Douek DC; Altmann DM; Clinical Sciences Centre, Royal
       Postgraduate Medical School,; Hammersmith Hospital, London, GB.
 SO    Eur J Immunol. 1995 Nov;25(11):3134-41. Unique Identifier : AIDSLINE
       MED/96085187
 AB    Major histocompatibility complex (MHC) class II genes are the strongest
       susceptibility markers for many human autoimmune diseases. A perplexing
       aspect of this is that HLA alleles can confer either susceptibility or
       dominant protection. In nonobese diabetic (NOD) mice, the strongest
       known diabetes susceptibility locus is within the MHC and is presumed to
       be the H-2Ag7 product. When NOD mice carry a transgenic E alpha d
       molecule allowing expression of an H-2E heterodimer, diabetes is
       prevented. We investigated whether, as in human autoimmunity, a single
       class II heterodimer might protect from some autoimmune diseases while
       predisposing to others. NOD mice are susceptible to experimental
       autoimmune encephalomyelitis (EAE) induced by the proteolipoprotein
       (PLP) epitope 56-70. Susceptibility to EAE was analyzed in NOD mice
       which either have or lack transgenic H-2E expression. We found that H-2E
       expression in NOD mice has converse effects on diabetes and EAE: while
       diabetes is prevented, EAE is greatly exacerbated and leads to
       demyelination. Although PLP 56-70 could be presented both in the context
       of H-2A and H-2E, increased disease severity in H-2E transgenic mice
       could not be attributed either to an enhanced T cell proliferative
       response to PLP or to differences in determinant spread. However,
       cytokine analysis of the response revealed important differences between
       NOD mice and their H-2E transgenic counterparts: H-2E expression was
       associated with reduced interleukin-4 secretion and enhanced
       interferon-gamma (IFN-gamma) secretion by lymph node cells, while the
       response of central nervous system infiltrating T cells displayed a
       markedly enhanced IFN-gamma response. Thus, whether a particular class
       II molecule confers resistance or susceptibility to an autoimmune
       disease may depend on differential cytokine profiles elicited by
       particular class II/autoantigen complexes.
 DE    Amino Acid Sequence  Animal  Cytokines/*BIOSYNTHESIS  Diabetes Mellitus,
       Insulin-Dependent/GENETICS/*PREVENTION &  CONTROL  Encephalomyelitis,
       Allergic/GENETICS/*PATHOLOGY  H-2 Antigens/*GENETICS  Mice  Mice, Inbred
       BALB C  Mice, Inbred NOD  Mice, Transgenic  Molecular Sequence Data
       Myelin Proteolipid Protein/GENETICS/IMMUNOLOGY  Support, Non-U.S. Gov't
       Th1 Cells/*METABOLISM  JOURNAL ARTICLE

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

