Abstract
Maternal decidual CD8+ T (dCD8+ T) cells must integrate the antithetical demands of maternal–fetal tolerance and anti-viral immunity to establish a successful pregnancy. T-cell immunoglobulin mucin-3 (Tim-3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two important co-inhibitory molecules that regulating CD8+ T cells responses during infection and tumor. In the present study, we examined the co-expression of Tim-3 and CTLA-4 on CD8+ T cells during pregnancy and found the higher frequency of Tim-3+CTLA-4+dCD8+ T cells in response to trophoblasts. This Tim-3+CTLA-4+dCD8+ T cells subset showed an active status and produced more anti-inflammatory cytokines. Furthermore, the decreased number and altered function of Tim-3+CTLA-4+dCD8+ T cells correlated to miscarriage. Combined blocking Tim-3 and CTLA-4 pathways were highly effective in inhibiting the production of anti-inflammatory cytokines and were detrimental to the maintenance of pregnancy. Together, these findings supported that Tim-3 and CTLA-4 pathways might play positive roles in the establishment and/or maintenance of maternal–fetal tolerance so to promote the maintenance of normal pregnancy. So the reproductive safety must be considered, especially when anti-Tim-3/CTLA-4 antibody (and other immune checkpoint inhibitors) are used in pregnancy.
| Original language | English (US) |
|---|---|
| Article number | 407 |
| Journal | Cell Death and Disease |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2019 |
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ASJC Scopus subject areas
- Immunology
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research
Cite this
The appropriate frequency and function of decidual Tim-3+CTLA-4+CD8+ T cells are important in maintaining normal pregnancy. / Wang, Songcun; Sun, Fengrun; Li, Mengdie; Qian, Jinfeng; Chen, Chunqin; Wang, Mingyan; Zang, Xingxing; Li, Dajin; Yu, Min; Du, Meirong.
In: Cell Death and Disease, Vol. 10, No. 6, 407, 01.06.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The appropriate frequency and function of decidual Tim-3+CTLA-4+CD8+ T cells are important in maintaining normal pregnancy
AU - Wang, Songcun
AU - Sun, Fengrun
AU - Li, Mengdie
AU - Qian, Jinfeng
AU - Chen, Chunqin
AU - Wang, Mingyan
AU - Zang, Xingxing
AU - Li, Dajin
AU - Yu, Min
AU - Du, Meirong
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Maternal decidual CD8+ T (dCD8+ T) cells must integrate the antithetical demands of maternal–fetal tolerance and anti-viral immunity to establish a successful pregnancy. T-cell immunoglobulin mucin-3 (Tim-3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two important co-inhibitory molecules that regulating CD8+ T cells responses during infection and tumor. In the present study, we examined the co-expression of Tim-3 and CTLA-4 on CD8+ T cells during pregnancy and found the higher frequency of Tim-3+CTLA-4+dCD8+ T cells in response to trophoblasts. This Tim-3+CTLA-4+dCD8+ T cells subset showed an active status and produced more anti-inflammatory cytokines. Furthermore, the decreased number and altered function of Tim-3+CTLA-4+dCD8+ T cells correlated to miscarriage. Combined blocking Tim-3 and CTLA-4 pathways were highly effective in inhibiting the production of anti-inflammatory cytokines and were detrimental to the maintenance of pregnancy. Together, these findings supported that Tim-3 and CTLA-4 pathways might play positive roles in the establishment and/or maintenance of maternal–fetal tolerance so to promote the maintenance of normal pregnancy. So the reproductive safety must be considered, especially when anti-Tim-3/CTLA-4 antibody (and other immune checkpoint inhibitors) are used in pregnancy.
AB - Maternal decidual CD8+ T (dCD8+ T) cells must integrate the antithetical demands of maternal–fetal tolerance and anti-viral immunity to establish a successful pregnancy. T-cell immunoglobulin mucin-3 (Tim-3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two important co-inhibitory molecules that regulating CD8+ T cells responses during infection and tumor. In the present study, we examined the co-expression of Tim-3 and CTLA-4 on CD8+ T cells during pregnancy and found the higher frequency of Tim-3+CTLA-4+dCD8+ T cells in response to trophoblasts. This Tim-3+CTLA-4+dCD8+ T cells subset showed an active status and produced more anti-inflammatory cytokines. Furthermore, the decreased number and altered function of Tim-3+CTLA-4+dCD8+ T cells correlated to miscarriage. Combined blocking Tim-3 and CTLA-4 pathways were highly effective in inhibiting the production of anti-inflammatory cytokines and were detrimental to the maintenance of pregnancy. Together, these findings supported that Tim-3 and CTLA-4 pathways might play positive roles in the establishment and/or maintenance of maternal–fetal tolerance so to promote the maintenance of normal pregnancy. So the reproductive safety must be considered, especially when anti-Tim-3/CTLA-4 antibody (and other immune checkpoint inhibitors) are used in pregnancy.
UR - http://www.scopus.com/inward/record.url?scp=85066306749&partnerID=8YFLogxK
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U2 - 10.1038/s41419-019-1642-x
DO - 10.1038/s41419-019-1642-x
M3 - Article
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 6
M1 - 407
ER -