Document 0137
 DOCN  M9650137
 TI    T cell-derived IL-3 induces the production of IL-4 by non-B, non-T cells
       to amplify the Th2-cytokine response to a non-parasite antigen in
       Schistosoma mansoni-infected mice.
 DT    9605
 AU    Kullberg MC; Berzofsky JA; Jankovic DL; Barbieri S; Williams ME;
       Perlmann P; Sher A; Troye-Blomberg M; Immunobiology Section, National
       Institute of Allergy and; Infectious Diseases (NIAID), National
       Institutes of Health,; Bethesda, MD 20892, USA.
 SO    J Immunol. 1996 Feb 15;156(4):1482-9. Unique Identifier : AIDSLINE
       MED/96164577
 AB    We describe a novel amplification mechanism underlying the increased
       early IL-4 production observed in Schistosoma mansoni-infected mice in
       response to a non-parasite Ag, sperm whale myoglobin (SwMb). Earlier
       studies have shown that splenic Fc epsilon R+ non-B, non-T (NBNT) cells
       from schistosome-infected mice secrete IL-4 after stimulation with
       parasite Ag. We now demonstrate that purified NBNT cells from
       SwMb-immunized S. mansoni-infected mice do not respond directly to SwMb,
       but produce IL-4 in response to IL-3. Accordingly, we show that the
       early SwMb-specific IL-4 response of spleen cells (SC) from immunized
       infected mice is dependent on IL-3 and on CD4+ T cells. Thus, most of
       the early SwMb-induced IL-4 from SC of infected mice appears to be
       produced by NBNT cells triggered by IL-3 synthesized by SwMb-specific
       CD4+ T cells. IL-3-induced IL-4 production was also observed in purified
       NBNT cells from immunized uninfected mice, but the frequency and/or
       IL-4-producing capacity of splenic IL-3-responsive cells was found to be
       8 to 16 times higher in immunized infected animals. IL-4 production by
       purified CD4+ cells from immunized infected mice was also seen after
       SwMb stimulation, but this response showed slower kinetics than those of
       total SC, was IL-3-independent, and on average threefold greater than
       that by CD4+ cells from immunized uninfected controls. Thus, increased
       SwMb-induced IL-4 production in immunized S. mansoni-infected mice
       results from direct synthesis by CD4+ T cells, as well as their
       stimulation via IL-3 of an expanded population of NBNT cells. The latter
       pathway may serve as an amplification loop for Th2-cytokine responses.
 DE    Animal  CD4-Positive T-Lymphocytes/IMMUNOLOGY  Female
       Interleukin-3/*PHYSIOLOGY  Interleukin-4/*BIOSYNTHESIS
       Lymphocytes/*IMMUNOLOGY  Mice  Mice, Inbred BALB C  Myoglobin/IMMUNOLOGY
       Receptors, IgG/PHYSIOLOGY  Schistosoma mansoni  Schistosomiasis
       mansoni/*IMMUNOLOGY  Spleen/CYTOLOGY  Support, Non-U.S. Gov't  Th2
       Cells/*IMMUNOLOGY  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).