       Document 0370
 DOCN  M9610370
 TI    Thymic selection and cell division.
 DT    9601
 AU    Ernst B; Surh CD; Sprent J; Department of Immunology, Scripps Research
       Institute, La Jolla,; California 92037, USA.
 SO    J Exp Med. 1995 Oct 1;182(4):961-71. Unique Identifier : AIDSLINE
       MED/96018796
 AB    Cell division during thymic selection was studied with a system in which
       purified populations of T cell antigen receptor (TCR)- CD4+8+
       (double-positive [DP]) cells and fetal thymic epithelial cells (TEC)
       were reaggregated in tissue culture. In this system, immature DP cells
       differentiate into mature single-positive (SP) CD4+8- and CD4-8+ TCRhi
       cells within 3-4 d, indicative of positive selection. By adding the DNA
       precursor, bromodeoxyuridine, to the cultures and staining cells for
       bromodeoxyuridine incorporation, T cell division in reaggregation
       cultures was found to be high on day 1, low on day 2, and high on days
       4-5. Cell separation studies established that cell division on day 1 was
       restricted to DP blast cells. In the absence of blast cells, small DP
       cells failed to proliferate and differentiated into SP cells without
       cell division, thus indicating that proliferation is not an essential
       component of positive selection. This applied to SP cells generated
       within the first 2-3 d. Surprisingly, the SP cells generated later in
       culture showed a high rate of cell division; the proliferating SP cells
       were TCRhi and included both CD4+8- and CD4-8+ cells. Turnover of TCRhi
       SP cells was also prominent in the normal neonatal thymus and in TEC
       reaggregation cultures prepared with adult lymph node T cells. We
       speculate that division of mature SP cells in the perinatal thymic
       microenvironment is driven by stimulatory cytokines released from TEC.
       Such proliferation could be a device to expand the mature T cell
       repertoire before export to the periphery.
 DE    Animal  Biological Markers  Bromodeoxyuridine/METABOLISM  Cell
       Aggregation  Cell Differentiation  *Cell Division  Cell Separation
       Cells, Cultured  CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Flow Cytometry  Mice  Mice, Inbred C57BL
       Receptors, Antigen, T-Cell/IMMUNOLOGY  *Selection (Genetics)  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/*IMMUNOLOGY
       Thymus Gland/CYTOLOGY/*IMMUNOLOGY  JOURNAL ARTICLE

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

