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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).