Document 0524
 DOCN  M9590524
 TI    Generation of antigen-specific CD4+ T cell lines from naive precursors.
 DT    9509
 AU    Mehta-Damani A; Markowicz S; Engleman EG; Department of Pathology,
       Stanford University School of Medicine,; Palo Alto, CA, USA.
 SO    Eur J Immunol. 1995 May;25(5):1206-11. Unique Identifier : AIDSLINE
       MED/95293012
 AB    The conditions required for sensitizing naive T cells to nominal antigen
       are poorly understood. In this report we describe an in vitro system for
       generating antigen-specific CD4+ T cells from previously unprimed
       individuals. Freshly isolated CD4+ T cells were cultured with keyhole
       limpet hemocyanin (KLH), sperm whale myoglobin (SWM), or human
       immunodeficiency virus (HIV) gp160, antigens to which most persons have
       not been sensitized, in the presence of either dendritic cells (DC) or
       macrophages (M phi). In short-term (< 8 days) cultures, CD4+ T cells or
       their CD4+, CD45RA (naive) subpopulation mounted significant
       proliferative responses to KLH, SWM, and HIV gp160, but only if the
       antigens were presented by DC. In contrast, CD4+, CD45RO (memory) T
       cells responded poorly to these antigens, although they responded
       vigorously to tetanus toxoid, a recall antigen, presented by either DC
       or M phi. KLH- and SWM-specific CD4+ T cell lines were established from
       the starting population that had been sensitized in vitro, following
       repeated stimulation with antigen and M phi in medium supplemented with
       interleukin-2 and interleukin-4. Despite the continued presence of these
       cytokines during T cell expansion, the expanded lines retained their
       ability to respond to the priming antigen in the absence of exogenous
       cytokines. When the CD45RA and CD45RO subpopulations were sensitized and
       expanded separately, the CD45RA cells alone gave rise to
       antigen-specific T cell lines, while the CD45RO cells proliferated
       nonspecifically. These results demonstrate that human naive CD4+ T cells
       can be sensitized in vitro to nominal antigens presented by DC and that
       the sensitized cells can be expanded into long-term lines that retain
       their antigen specificity.
 DE    Animal  *Antigen Presentation  Antigens/*IMMUNOLOGY  Antigens,
       CD45/ANALYSIS  Comparative Study  CD4-Positive
       T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY  Dendritic Cells/*IMMUNOLOGY  Gene
       Products, env/IMMUNOLOGY  Hemocyanin/IMMUNOLOGY  Human
       Macrophages/IMMUNOLOGY  Myoglobin/IMMUNOLOGY  Protein
       Precursors/IMMUNOLOGY  Support, U.S. Gov't, Non-P.H.S.  Support, U.S.
       Gov't, P.H.S.  T-Lymphocyte Subsets/*IMMUNOLOGY  Whales  JOURNAL ARTICLE

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