Document 0412
 DOCN  M9610412
 TI    Down-regulation of CD8 on mature antigen-reactive T cells as a mechanism
       of peripheral tolerance.
 DT    9601
 AU    Zhang L; Fung-Leung W; Miller RG; Ontario Cancer Institute, University
       of Toronto, Ontario, Canada.
 SO    J Immunol. 1995 Oct 1;155(7):3464-71. Unique Identifier : AIDSLINE
       MED/96015991
 AB    Previously we have shown that intravenous injection of male B6
       lymphocytes containing CD8+ cells into B6 female anti-HY TCR transgenic
       mice results at 6 wk in the disappearance of the majority of male
       Ag-reactive T cells (TghighCD8+) from the periphery. Here we investigate
       the process in more detail. B6 female anti-HY TCR transgenic mice were
       intravenously injected with viable lymphocytes from male B6 normal,
       CD4-/-, CD8-/- or CD8-/- carrying a CD8 transgene lacking its
       cytoplasmic tail (CD8 tail-less) mice. The fate of TghighCD8+ cells was
       followed in vivo. There was always a large (at least twofold) expansion
       of these cells in the periphery 4 days after encountering male Ag. Their
       subsequent fate differed, however, depending on whether or not the
       injected male lymphocytes contained normal CD8-expressing cells. If the
       injected male lymphocytes contained normal CD8 cells, at 6 wk there was
       a large drop in the number of TghighCD8+ cells associated with a rise in
       the number of TghighCD8- cells. If the injected male lymphocytes lacked
       CD8 cells or expressed only tail-less CD8, TghighCD8+ cell numbers
       returned to normal by 6 wk, while TghighCD8- cell numbers remained
       unchanged. The TghighCD8- cells, although carrying high levels of the
       male specific TCR, did not react to male Ag. In addition, their ability
       to respond in anti-CD3-induced activation, which does not require CD8 as
       a co-receptor, was significantly impaired. Our data suggest that
       down-regulation of CD8 on the Ag-reactive T cells accounts, at least
       partially, for the disappearance of HY-reactive T cells from the
       periphery. Further, some step in the process requires signaling through
       the cytoplasmic domain of CD8 on the injected Ag-bearing cells.
 DE    Animal  Antigen Presentation  Antigens, CD8/*ANALYSIS  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  Down-Regulation (Physiology)  Female
       *Immunocompetence  Male  Mice  Mice, Transgenic  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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