       Document 0113
 DOCN  M9610113
 TI    Alloantigen priming after total lymphoid irradiation alters alloimmune
       cytokine responses.
 DT    9601
 AU    Field EH; Rouse TM; Department of Medicine, University of Iowa College
       of Medicine,; Iowa City, USA.
 SO    Transplantation. 1995 Oct 15;60(7):695-702. Unique Identifier : AIDSLINE
       MED/96029805
 AB    Total lymphoid irradiation (TLI) treatment represents a model of
       acquired tolerance, as TLI-treated mice develop donor-specific tolerance
       when exposed to alloantigens shortly after completing TLI. To determine
       whether immunoredirection plays a role in immunologic tolerance in TLI,
       we examined whether antigen priming in the immediate post-TLI stage
       altered the cytokine profile toward Th2. Compared with splenocytes
       isolated from control primed mice, the splenocytes from TLI-primed mice
       failed to proliferate to immunogen in mixed leukocyte reaction cultures
       but proliferated normally to third-party alloantigen. Whole spleen and
       purified CD4 cells isolated from TLI-primed mice produced more
       interleukin (IL)-4 and less gamma-interferon (IFN-gamma) in response to
       immunogen-bearing stimulator cells than controls, resulting in higher
       IL-4 to IFN-gamma ratios. The CD4 subset from TLI-primed mice contained
       more IL-4-producing and fewer IFN-gamma-producing cells, suggesting that
       priming after TLI shifted CD4 maturation toward Th2 cells. Surprisingly,
       TLI-primed mice contained no immunogen-responsive, IFN-gamma-producing
       CD8 cells, indicating that priming after TLI abrogated development of
       this CD8 subset. In summary, the data show that priming in the immediate
       post-TLI phase shifts the allospecific memory cytokine pattern toward
       Th2 cytokines by enhancing IL-4-producing CD4 cells and preventing
       maturation of IFN-gamma-producing CD8 cells. We speculate that the
       cytokine milieu at the time of antigen priming drives differentiation of
       the tolerogen-specific immune response toward Th2 cells, because
       splenocytes isolated immediately after TLI produced high levels of IL-4
       and little IL-2. The enhanced Th2 pattern that developed in the
       TLI-primed mice suggests that immunoredirection may also occur in the
       TLI model of tolerance.
 DE    Animal  Cell Differentiation/PHYSIOLOGY  Comparative Study
       Cytokines/*BIOSYNTHESIS/IMMUNOLOGY  CD4-Positive
       T-Lymphocytes/CYTOLOGY/IMMUNOLOGY/*METABOLISM  CD8-Positive
       T-Lymphocytes/CYTOLOGY/IMMUNOLOGY/*METABOLISM  Enzyme-Linked
       Immunosorbent Assay  Female  Immune Tolerance  Isoantigens/*IMMUNOLOGY
       *Lymphatic Irradiation  Male  Mice  Mice, Inbred AKR  Mice, Inbred BALB
       C  Mice, Inbred C57BL  Support, U.S. Gov't, Non-P.H.S.  Support, U.S.
       Gov't, P.H.S.  Th1 Cells/CYTOLOGY/IMMUNOLOGY/METABOLISM  Th2
       Cells/CYTOLOGY/IMMUNOLOGY/METABOLISM  JOURNAL ARTICLE

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

