Document 0105
 DOCN  M9550105
 TI    T cell genetic background determines default T helper phenotype
       development in vitro.
 DT    9505
 AU    Hsieh CS; Macatonia SE; O'Garra A; Murphy KM; Department of Pathology,
       Washington University School of; Medicine, St. Louis, Missouri 63110.
 SO    J Exp Med. 1995 Feb 1;181(2):713-21. Unique Identifier : AIDSLINE
       MED/95138703
 AB    A host's ability to resist certain pathogens such as Leishmania major
       can depend upon the phenotype of T helper (Th) subset that develops.
       Different murine genetic backgrounds are known to significantly alter
       the direction of Th subset development, although the cellular basis of
       this influence is poorly understood. To examine the basis of this effect
       we used an in vitro alpha/beta-T cell receptor (TCR) transgenic system
       for analysis of Th phenotype development. To control for TCR usage, we
       derived the DO11.10 alpha/beta-TCR transgene in several genetic
       backgrounds. Our findings suggest that the effects of genetic background
       on Th phenotype development reside within the T cell, and not the
       antigen-presenting cell compartment. Transgenic T cells from both the
       B10.D2 and BALB/c backgrounds showed development toward either the Th1
       or Th2 phenotype under the strong directing influence of interleukin
       (IL) 12 and IL4, respectively. However, when T cells were activated in
       vitro under neutral conditions in which exogenous cytokines were not
       added, B10.D2-derived T cells acquired a significantly stronger Th1
       phenotype than T cells from the BALB/c background, correspondent with in
       vivo Th responses to Leishmania in these strains. Importantly, these
       cytokine differences resulted in distinct functional properties, because
       B10.D2- but not BALB/c-derived T cells could induce macrophage
       production of nitric oxide, an important antimicrobial factor. Thus, the
       genetically determined default Th phenotype development observed in
       vitro may correspond to in vivo Th subset responses for pathogens such
       as Leishmania which do not initiate strong Th phenotype-directing
       signals.
 DE    Animal  Antibody-Producing Cells/IMMUNOLOGY  Cell
       Differentiation/GENETICS  Cells, Cultured  Leishmania major/*IMMUNOLOGY
       Macrophages/IMMUNOLOGY  Mice  Mice, Inbred BALB C  Mice, Inbred C57BL
       Mice, Transgenic  Nitric Oxide/BIOSYNTHESIS  Phenotype  Receptors,
       Antigen, T-Cell, alpha-beta/GENETICS  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).