provide greater understanding of how naïve
and memory T cell repertoires are main-
tained and persist in normal and patholog-
ical conditions.
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ACKNOWLEDGMENTS
We thank S. Ma for the statistical discussions in our study. We
thank C. Brennick and B. Cadugan for editing the manuscript and
staff members at the Yale Genome Editing Center, Yale Center for
Zhenget al., Science 376 , 996–1001 (2022) 27 May 2022 5of6
**
0
5
10
15
IFNγ
+ %
of
CD8
+ T cells
CD69
+ %
of CD8
+ T
cells
A B
E
0
5
10
15
CD
1
CD8
+ T cell number
(×10
6 )
*
control 9B12
lymph node
0
2
3
4
**
spleen
control 9B12
lymph node
ns
control 9B12
1
CD4
+ T cell number
(×10
6 )
0
2
3
4
5
0
5
10
15
spleen
ns
control 9B12
control 9B12
****
control 9B12
0
10
20
30
40 ****
lymph node
control 9B12
0
5
10
15
20
(^25) ****
spleen
control 9B12
2
0
4
6
8
lymph node
control 9B12
*
0
5
10
15
spleen
control 9B12
0
10
20
(^30)
lymph node
control 9B12
CD8
- %
4
5
6
7
8
9 **
spleen
control 9B12
CD8 - %
5
CD8 - T cell number
(×10
6 )
4
6
7
8
CD8 - %
CD8 - %
CD8 - T cell number
(×10
6 )
CD8 - T cell number
(×10
6 )
0
5
10
15
20
25
ns
lymph node
control 9B12
CD4 - %
0
5
10
15
20
ns
spleen
control 9B12
CD4 - %
CD4 - T cell number
(×10
6 )
Fig. 4. Blockade of PILRa–CD8ainteractions disrupts CD8+T cell homeostasis
and quiescence.(A) B6 WT mice were administered 200mg of control or
9B12 antibody intraperitoneally (i.p.) every 3 to 4 days starting on day 0. The
frequency and the absolute number of CD8+T cells among lymph node and
spleen cells were examined on day 15. (B andC) Thymectomized B6 WT mice
were administered 200mg of control or 9B12 antibody i.p. every 3 days starting
from day 0. CD8+T cell frequency and cell number (B), and CD4+Tcellfrequency
and cell number (C) in the lymph node and spleen were examined on day 14.
(D) One day after 200mg of control or 9B12 antibody was administered to B6 WT
mice i.p., lymph node CD8+T cells were analyzed for CD69 expression by
flow cytometry. (E) One day after 200mg of control or 9B12 antibody was
administered to B6 WT mice i.p., CD8+T cells purified from lymph node cells
were stimulated by phorbol 12-myristate 13-acetate (PMA), ionomycin, and
brefeldin A and analyzed for IFN-gexpression by flow cytometry. Representative
data of two [(B) and (C)], three [(A) and (E)], and eight (D) independent
experiments are shown.n = 3 mice per group in (B), (C), (D), and (E).n = 5 mice
per group in (A). Mean ± SD is shown. *P< 0.05, P< 0.01, **P< 0.0001
by unpaired Student’s t test. ns, not significant.
RESEARCH | REPORT