These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Oligoclonal expansion of CTLs directed against a restricted number of dominant minor histocompatibility antigens in hemopoietic chimeras.
    Author: Brochu S, Baron C, Hétu F, Roy DC, Perreault C.
    Journal: J Immunol; 1995 Dec 01; 155(11):5104-14. PubMed ID: 7594519.
    Abstract:
    To understand how T cells respond to allogeneic minor histocompatibility Ags (MiHAs), we studied the fate of Thy-1.1+ lymphocytes, as well as their TCR usage and functional activity, in irradiated LP (Thy-1.2+) recipients transplanted with a mixture of C57BL/6 (Thy-1.2+) hemopoietic progenitors supplemented with either low or high numbers of B6.PL lymphocytes (Thy-1.1+). Mice transplanted with low numbers of T cells experienced a dramatic expansion (> or = 10(5)-fold) of donor Thy-1.1+/CD8+ cells during the first 15 days post-transplant. Flow-cytometric analysis and sequencing of junctional nucleotide sequences showed that the nature of this expansion was oligoclonal and involved primarily one or a few clones using V beta 5.1 or V beta 8.1 TCR elements. Expanded T lymphocyte populations displayed MHC-restricted cytotoxicity for a restricted number of MiHAs, that were found in only two peaks following fractionation of LP MiHAs by reverse-phase HPLC. Expansion of donor T cells was limited to the spleen, and short-lived in these recipients that became healthy long-term chimeras without any signs of graft-vs-host disease (GVHD). In contrast, mice transplanted with high numbers of T cells (GVHD+) showed proliferation of Thy-1.1+ donor cells not only in the spleen, but also in the thymus, and recipients died rapidly of GVHD. These results show that: 1) in the MiHA-incompatible transplantation setting, lack of GVHD cannot be explained simply by the absence of antihost T cell responses, 2) GVHD+ recipients present a massive thymic infiltration by donor mature T lymphocytes, and 3) antihost T cell responses are oligoclonal in nature and targeted to only a few MiHAs. These findings shed new light on the pathogenetic mechanisms involved in GVHD and on the selection of the T cell repertoire involved in response to immunodominant MiHAs.
    [Abstract] [Full Text] [Related] [New Search]