Document 0415
 DOCN  M9550415
 TI    Parameters controlling the programmed death of mature mouse T
       lymphocytes in high-dose suppression.
 DT    9505
 AU    Critchfield JM; Zuniga-Pflucker JC; Lenardo MJ; Laboratory of
       Immunology, National Institute of Allergy and; Infectious Diseases,
       National Institutes of Health, Bethesda,; Maryland 20892.
 SO    Cell Immunol. 1995 Jan;160(1):71-8. Unique Identifier : AIDSLINE
       MED/95144752
 AB    We have characterized parameters of both T cells and antigen-presenting
       cells (APCs) that influence high-dose suppression due to apoptosis.
       Blockade of interleukin-2 (IL-2) utilization is shown to inhibit both
       proliferation and the ensuing death. An analysis of sublines of a mature
       T cell clone demonstrates a correlation between IL-2 receptor alpha
       chain (IL-2R) induction, increased proliferation, and greater
       suppression at high antigen doses. Profound loss of cells at high
       antigen dose was found to require at least 48 to 72 hr to develop.
       Antigen add-back experiments showed that strong T cell receptor
       reengagement of activated, cycling cells was essential for proliferative
       suppression and cell loss. Increasing the ratio of APC:T lymphocytes to
       50:1 augmented cell death. For antigen-induced death of lymph node T
       cells, fresh T-depleted splenocytes were more effective than splenocytes
       that had been irradiated or treated with mitomycin C. Thus, T lymphocyte
       apoptosis at high antigen doses is a function of the activation response
       of the T lymphocyte as well as the efficiency of antigen presentation by
       the APC. These results strengthen the theory that apoptosis takes part
       in a feedback regulatory mechanism that has been called propriocidal
       regulation, which limits T cell expansion at high antigen doses.
 DE    Animal  Antigen-Presenting Cells/*IMMUNOLOGY  Apoptosis/*IMMUNOLOGY
       Clone Cells  Encephalitogenic Basic Proteins/IMMUNOLOGY  Flow Cytometry
       Immune Tolerance/*PHYSIOLOGY  Lymphocyte Transformation/IMMUNOLOGY  Mice
       Mice, Transgenic  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/*IMMUNOLOGY  Th1 Cells/IMMUNOLOGY  JOURNAL ARTICLE

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