       Document 0960
 DOCN  M9540960
 TI    The abnormal lpr double-negative T cell fails to proliferate in vivo.
 DT    9504
 AU    Sobel ES; Kakkanaiah VN; Rapoport RG; Eisenberg RA; Cohen PL; Department
       of Medicine, University of Florida, Gainesville 32610.
 SO    Clin Immunol Immunopathol. 1995 Feb;74(2):177-84. Unique Identifier :
       AIDSLINE MED/95129295
 AB    Mice homozygous for the autosomal recessive gene lpr develop marked
       lymphadenopathy and a systemic autoimmune disease resembling human
       systemic lupus erythematosus. The enlarged nodes are dominated by T
       cells with an unusual surface phenotype: dull Thy-1+, dull CD3+, CD4-,
       CD8-, B220+ (double-negative T cells or DNTs). Despite their massive
       accumulation in vivo, these cells fail to proliferate in response to
       conventional T-cell mitogens in vitro. The identification of the lpr
       mutation as a defect in the Fas apoptosis receptor gene suggests that
       DNT accumulation may result from abnormal persistence rather than
       overproliferation. To test in vivo whether DNTs persist abnormally or
       have a capacity to differentiate into single-positive T cells, we have
       performed cell transfer experiments between congenic strains of lpr and
       +/+ mice differentially marked by expression of the Ly-1 or Thy-1
       alleles. Although transferred lpr lymph node cells were mostly DNTs at
       the time of injection, most recovered cells of donor origin were single
       positive, particularly CD8+, at all time points after transfer.
       Furthermore, transfer of purified DNTs resulted in recovery of
       relatively few cells of donor origin. Transfer of lpr T cells enriched
       for CD8 expression confirmed the preferential survival of this subset.
       Thus, DNTs are a surprisingly transient population and have little
       capacity for transformation to single positives. This would suggest that
       DNTs are constantly being renewed, perhaps from CD4+ and CD8+
       precursors.
 DE    Animal  Cell Differentiation/GENETICS  Cell Survival/GENETICS
       CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Flow Cytometry  Immunophenotyping
       Immunotherapy, Adoptive  Lymph Nodes/CYTOLOGY  Lymphatic
       Diseases/GENETICS/*IMMUNOLOGY  *Lymphocyte Transfusion  Mice  Mice,
       Mutant Strains  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       T-Lymphocyte Subsets/*IMMUNOLOGY/TRANSPLANTATION  Thymectomy  JOURNAL
       ARTICLE

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

