       Document 0048
 DOCN  M9630048
 TI    CD4 Th2 cells do not functionally suppress CTL generation in neonatal
       tolerant mice.
 DT    9603
 AU    Gao Q; Chen N; Field EH; Department of Medicine, University of Iowa
       College of Medicine,; Iowa City, USA.
 SO    Transplantation. 1995 Dec 15;60(11):1260-8. Unique Identifier : AIDSLINE
       MED/96106486
 AB    Injecting semiallogeneic CAF1 spleen into BALB/c newborn mice renders
       mice tolerant, and the majority of mice show prolonged survival of
       tolerogen-bearing A/J skin grafts. Moreover, graft survival is
       associated with enhanced Th2 cytokine responses and graft rejection with
       Th1 cytokine responses. To further delineate the mechanisms of
       tolerance, we evaluated CTL responses and found that 74% of neonatal
       primed mice failed to generate A/J-specific CTL responses, as determined
       by standard CTL assays and pTc3 frequency analyses. CTL unresponsiveness
       coexisted with an enhanced tolerogen-specific Th2 memory cytokine
       profile; spleen cells from neonatal primed mice secreted more
       interleukin (IL)-4 and less IL-2 and interferon (IFN)-gamma in MLR
       cultures compared with either adult primed or naive controls. We
       therefore examined the hypothesis that enhanced Th2 cytokine levels
       prevent the generation of tolerogen-specific CTL. Adding neutralizing
       antibodies to IL-4 and IL-10 recovered IFN-gamma production in vitro but
       not A/J-specific CTL response. In addition, CD4 cells from neonatal
       primed mice provided help for primary or secondary CD8 CTL generation,
       which suggests that the enhanced Th2 cytokine profile does not actively
       suppress CTL generation. Furthermore, CD4 cells from adult primed mice
       failed to restore the A/J-specific CD8 CTL generation of neonatal primed
       mice. The results show that failure to develop A/J-specific CTL reaction
       occurs without suppression by the enhanced Th2-type responses and imply
       that either deletion or anergy mechanisms block CTL generation.
       Therefore, neonatal alloantigen exposure not only shifts the development
       of alloreactive CD4 cells toward Th2, but also blocks development of
       alloreactive CD8 CTL in this strain combination.
 DE    Animal  Animals, Newborn/*IMMUNOLOGY  Cells, Cultured
       Cytokines/METABOLISM  CD8-Positive T-Lymphocytes/IMMUNOLOGY  Female
       *Immune Tolerance  Immunity, Cellular  Interferon Type II/METABOLISM
       Lymphocyte Cooperation  Lymphocyte Culture Test, Mixed  Male  Mice
       Mice, Inbred A  Mice, Inbred BALB C  Mice, Inbred C57BL  Rabbits
       Spleen/CYTOLOGY  Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't,
       P.H.S.  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  Th2 Cells/*IMMUNOLOGY
       JOURNAL ARTICLE

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

