       Document 0027
 DOCN  M9640027
 TI    Direct evidence for in vivo induction of CD8+ cytotoxic T cells directed
       to donor MHC class I peptides following mouse allotransplantation.
 DT    9604
 AU    Popov IA; Fedoseyeva EV; Orr PL; Garovoy MR; Benichou G; Department of
       Surgery, University of California San Francisco; 94143-0508, USA.
 SO    Transplantation. 1995 Dec 27;60(12):1621-4. Unique Identifier : AIDSLINE
       MED/96125859
 AB    There is accumulating evidence indicating that the T cell response to
       donor major histocompatibility complex (MHC) peptides plays a crucial
       role in graft rejection. We and others previously demonstrated the
       involvement of MHC class-II-restricted recognition of donor MHC class I
       and II peptides by alloreactive CD4+ T helper cells in graft rejection.
       Here we studied the in vivo induction of CD8+ cytotoxic T lymphocytes
       (CTL) directed to donor MHC class I peptides following
       allotransplantation in the mouse. To address this question, BALB/c
       irradiated splenocytes (H-2d) (Kd, A(d), E(d), Ld, Dd) were injected
       into Ld-deficient BALB/c-dm2 (dm2) mutant mice (Kd, A(d), E(d), -, Dd).
       Nine days after allogeneic cell transplant, recipient lymph node T cells
       were tested for cytolytic activity using peritoneal macrophages as
       targets. We observed that in addition to BALB/c targets, dm2 macrophages
       could also be lysed but only when incubated with a dominant peptide on
       donor Ld molecule, Ld 61-80. This response was abolished by anti-CD8 but
       not anti-CD4 monoclonal antibodies. In addition, after immunization of
       dm2 mice with the peptide Ld 61-80, alloreactive CTL were generated in
       vivo and shown to destroy allogeneic donor BALB/c target cells in the
       absence of exogenously added peptide. We conclude that after
       allotransplantation, concomitant in vivo priming of alloreactive CD8+
       CTL by donor MHC class I peptides occurs through both direct and
       indirect pathways of allorecognition.
 DE    Animal  Antigen Presentation  Cell Transplantation  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  Histocompatibility Antigens Class
       I/*IMMUNOLOGY  Lymphocyte Transformation/IMMUNOLOGY  Mice  Mice, Inbred
       BALB C  Spleen/CYTOLOGY/IMMUNOLOGY  Support, U.S. Gov't, P.H.S.
       Transplantation, Homologous/*IMMUNOLOGY  JOURNAL ARTICLE

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

