Document 0470
 DOCN  M9620470
 TI    The effect of antigen dose on CD4+ T helper cell phenotype development
       in a T cell receptor-alpha beta-transgenic model.
 DT    9602
 AU    Hosken NA; Shibuya K; Heath AW; Murphy KM; O'Garra A; Department of
       Immunology, DNAX Research Institute, Palo Alto,; California 94304, USA.
 SO    J Exp Med. 1995 Nov 1;182(5):1579-84. Unique Identifier : AIDSLINE
       MED/96042155
 AB    The dose of foreign antigen can influence whether a cell-mediated or
       humoral class of immune response is elicited, and this may be largely
       accounted for by the development of CD4+ T helper cells (Th) producing
       distinct sets of cytokines. The ability of antigen dose to direct the
       development of a Th1 or Th2 phenotype from naive CD4+ T cells, however,
       has not been demonstrated. In this report, we show that the antigen dose
       used in primary cultures could directly affect Th phenotype development
       from naive DO11.10 TCR-alpha beta-transgenic CD4+ T cells when dendritic
       cells or activated B cells were used as the antigen-presenting cells.
       Consistent with our previous findings, midrange peptide doses (0.3-0.6
       microM) directed the development of Th0/Th1-like cells, which produced
       moderate amounts of interferon gamma (IFN-gamma). As the peptide dose
       was increased, development of Th1-like cells producing increased amounts
       of IFN-gamma was initially observed. At very high (> 10 microM) and very
       low (< 0.05 microM) doses of antigenic peptide, however, a dramatic
       switch to development of Th2-like cells that produced increasing amounts
       of interleukin 4 (IL-4) and diminishing levels of IFN-gamma was
       observed. This was true even when highly purified naive, high buoyant
       density CD4+ LECAM-1hi T cells were used, ruling out a possible
       contribution from contaminating memory phenotype CD4+ T cells.
       Neutralizing anti-IL-4 antibodies completely inhibited the development
       of this Th2-like phenotype at both high and low antigen doses,
       demonstrating a requirement for endogenous IL-4. Our findings suggest
       that the antigen dose may affect the levels of endogenous cytokines such
       as IL-4 in primary cultures, resulting in the development of distinct Th
       cell phenotypes.
 DE    Animal  Antigen Presentation  B-Lymphocytes/IMMUNOLOGY  Dendritic
       Cells/IMMUNOLOGY  Dose-Response Relationship, Immunologic  Female
       Histocompatibility Antigens Class II/IMMUNOLOGY  Immunologic Memory
       Interferon Type II/*BIOSYNTHESIS  Interleukin-4/*BIOSYNTHESIS
       L-Selectin/IMMUNOLOGY  Mice  Mice, Inbred BALB C  Mice, Transgenic
       Phenotype  Receptors, Antigen, T-Cell, alpha-beta/GENETICS/*IMMUNOLOGY
       Support, Non-U.S. Gov't  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).