Document 0024
 DOCN  M9580024
 TI    In vivo depletion of CD8+ T cells results in Th2 cytokine production and
       alternate mechanisms of allograft rejection.
 DT    9506
 AU    Chan SY; DeBruyne LA; Goodman RE; Eichwald EJ; Bishop DK; Department of
       Surgery, University of Michigan School of Medicine,; Ann Arbor 48109,
       USA.
 SO    Transplantation. 1995 Apr 27;59(8):1155-61. Unique Identifier : AIDSLINE
       MED/95250170
 AB    A current hypothesis states that Th1 cytokines promote allograft
       rejection and that Th2 cytokines promote graft acceptance. We present
       data that question the tolerogenic activity of Th2 cytokines, and we
       suggest that Th2 cytokines may evoke allograft rejection by recruitment
       of alternate effector mechanisms. Unmodified rejection of mouse
       heterotopic cardiac allografts is associated with the accumulation of
       large numbers of donor-reactive CD8+ CTL within the allograft, which is
       indicative of a Th1-driven cellular response. However, when recipients
       are depleted of CD8+ CTL, rejection still occurs and is associated with
       an aggressive cellular infiltrate rich in eosinophils, large mononuclear
       cells, and fibroblast-like cells. Eosinophils, which are responsive to
       the Th2 cytokines IL-4 and IL-5, are not present in unmodified rejecting
       allografts. Differential production of Th1 versus Th2 cytokines was
       further suggested by altered levels of IgG2a (promoted by IFN gamma) and
       IgG1 (promoted by IL-4) alloantibody in the sera of these mice; IgG2a
       dominated the alloantibody response in unmodified allograft recipients,
       whereas IgG1 levels increased in recipients depleted of CD8+ CTL.
       Altered intragraft cytokine gene expression was verified by RT-PCR; Th1
       (IL-2, IFN gamma), but not Th2 (IL-4, IL-5, IL-10), cytokine mRNAs were
       readily detectable in the allografts of unmodified recipients. In
       contrast, both Th1 and Th2 cytokine genes were expressed in the
       allografts of mice depleted of CD8+ CTL. These data suggest that
       donor-reactive CD8+ CTL inhibit intragraft production of Th2 cytokines,
       thereby promoting a Th1 dominated-rejection response. Elimination of
       CD8+ cells allows Th2 cytokine production, which may have deleterious,
       rather than protective, effects.
 DE    Animal  Base Sequence  Cytokines/*BIOSYNTHESIS  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  DNA Primers  Eosinophils/IMMUNOLOGY/PATHOLOGY
       Female  Gene Expression  Graft Rejection/*IMMUNOLOGY/PATHOLOGY  Graft
       Survival/*IMMUNOLOGY  Heart Transplantation/*IMMUNOLOGY/PATHOLOGY
       IgG/BIOSYNTHESIS  Interferon Type II/BIOSYNTHESIS
       Interleukins/BIOSYNTHESIS  *Lymphocyte Depletion  Mice  Mice, Inbred
       C57BL  Mice, Inbred DBA  Molecular Sequence Data  Polymerase Chain
       Reaction  Support, U.S. Gov't, P.H.S.  T-Lymphocytes,
       Cytotoxic/*IMMUNOLOGY  Transplantation, Homologous  JOURNAL ARTICLE

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