Document 0717
 DOCN  M9440717
 TI    In vitro maturation of human neonatal CD4 T lymphocytes. I. Induction of
       IL-4-producing cells after long-term culture in the presence of IL-4
       plus either IL-2 or IL-12.
 DT    9404
 AU    Wu CY; Demeure CE; Gately M; Podlaski F; Yssel H; Kiniwa M; Delespesse
       G; University of Montreal, Notre-Dame Hospital Research Center,; Canada.
 SO    J Immunol. 1994 Feb 1;152(3):1141-53. Unique Identifier : AIDSLINE
       MED/94132609
 AB    Recent studies in the mouse have established that IL-4 and IL-12 direct
       the development of Ag-stimulated naive CD4 T cells into, respectively,
       type 2 and type 1 Th cells. We report that prolonged exposure of
       immunologically naive and unstimulated human neonatal CD4 T cells to
       IL-4 or to IL-4 plus either IL-2 or IL-12 markedly affects their
       cytokine production on primary stimulation with PMA and ionomycin. IL-4
       induces long-term proliferation of neonatal T cells and after 3 wk of
       culture these are capable of producing high levels of Th1 (IL-2,
       IFN-gamma) but no Th2 (IL-4, IL-5) cytokines; IL-4-primed cells are
       homogenously CD45RO-/RA+ and CD31+. After culture in the presence of
       IL-4 + IL-2 or IL-4 + IL-12, neonatal T cells are enriched in CD45RO+
       and CD31- cells and they can produce Th2 as well as Th1 cytokines. In
       response to primary stimulation with PMA and ionomycin, cells primed
       with IL-4 + IL-2 produce IL-4, IL-5, and IL-10 and the same levels of
       IL-2 and IFN-gamma as IL-4-primed cells. Cells primed with IL-4 + IL-12
       produce very high levels of both IL-4 and IFN-gamma but no IL-5.
       Endogenous IFN-gamma that is detected in primary cultures containing
       IL-4 + IL-12 does not inhibit, but rather enhances, the ability of the
       cells to produce IL-4. Further analysis of IL-4 + IL-12-primed cells
       reveals that IL-4 is mainly produced by CD31- cells and that these cells
       can trigger B cells to synthesize Ig including IgE. Finally, positively
       selected CD31+ cells remain CD31+ and are poor IL-4 producers after 3 wk
       of culture with IL-4 + IL-12, suggesting that these two cytokines
       promote the selective expansion of the small number of CD31- cells that
       are present in freshly isolated neonatal CD4 T cells.
 DE    Adult  Antigens, CD/ANALYSIS  Antigens, Differentiation,
       Myelomonocytic/ANALYSIS  Cells, Cultured  CD4-CD8 Ratio  Human
       Immunophenotyping  In Vitro  Infant, Newborn  Interferon Type
       II/BIOSYNTHESIS  Interleukin-2/PHARMACOLOGY
       Interleukin-4/BIOSYNTHESIS/PHARMACOLOGY  Interleukins/PHARMACOLOGY
       Membrane Glycoproteins/ANALYSIS  Support, Non-U.S. Gov't  T-Lymphocytes,
       Helper-Inducer/*CYTOLOGY  Time Factors  T4 Lymphocytes/*CYTOLOGY
       JOURNAL ARTICLE

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