       Document 0049
 DOCN  M9630049
 TI    Expansion of memory Th2 cells over Th1 cells in neonatal primed mice.
 DT    9603
 AU    Chen N; Gao Q; Field EH; Department of Medicine, University of Iowa
       College of Medicine,; Iowa City 52246, USA.
 SO    Transplantation. 1995 Dec 15;60(11):1187-93. Unique Identifier :
       AIDSLINE MED/96106474
 AB    BALB/c mice primed with CAF1 splenocytes during the neonatal stage
       developed A/J-specific tolerance with prolonged survival (> 60 days) of
       A/J skin grafts. Mice failed to develop A/J-specific cytotoxicity, but
       rejected third-party skin grafts and generated appropriate third-party
       cytotoxic T cell responses. We demonstrated previously that graft
       acceptance was associated with enhanced interleukin (IL)-4 and
       diminished interferon [IFN]-gamma tolerogen-specific cytokine
       production, whereas third-party graft rejection was associated with the
       opposite pattern of cytokine production. We now report that neonatal
       mice do not mount mixed lymphocyte reaction responses against A/J, but
       the mice contain a higher percentage of IL-4-producing cells that were
       characterized as CD4+Mel-14lo cells. Although alloantigen priming of
       both neonatal and adult control mice expands the CD4+Mel-14lo subset,
       CD4+Mel-14lo cells from neonatal primed mice produce significantly
       higher levels of IL-4 and IL-10 and lower IFN-gamma, whereas
       CD4+Mel-14lo cells from adult primed mice produce mainly IFN-gamma.
       Moreover, enzyme-linked spot immunosorption analysis demonstrates that,
       compared with adult primed mice, neonatal primed mice contain more
       IL-4-producing CD4 cells and less IFN-gamma-producing cells, which
       indicates that neonatal antigen exposure induces and expands
       alloreactive Th2 memory CD4 cells. The addition of neutralizing
       antibodies against IL-4 and IL-10 to primary MLR failed to recover
       IFN-gamma by CD4+Mel-14lo cells, but cells secreted IFN-gamma after a
       second in vitro restimulation with tolerogen, which indicates that CD4
       cells from neonatal tolerant mice have the capacity to differentiate
       into Th1 cells. In summary, neonatal tolerant mice contain higher ratios
       of Th2/Th1 CD4 cells, and the Th2 cytokines function to maintain the
       ratio by inhibiting Th1 differentiation.
 DE    Animal  Animals, Newborn/*METABOLISM  CD4 Lymphocyte Count  *Immune
       Tolerance  Immunologic Memory  Interferon Type II/BIOSYNTHESIS
       Interleukin-4/BIOSYNTHESIS  Lymphocyte Transformation  Mice  Mice,
       Inbred A  Mice, Inbred BALB C  Support, U.S. Gov't, Non-P.H.S.  Support,
       U.S. Gov't, P.H.S.  T-Lymphocyte Subsets/CYTOLOGY  Th2 Cells/*CYTOLOGY
       JOURNAL ARTICLE

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

