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1996-01-30
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).