Antigen-specific decidual CD8+ T cells include distinct effector memory and tissue-resident memory cells.

Area of Science:

• Immunology
• Reproductive immunology
• Maternal-fetal interface immunology

Background:

• Maternal decidual CD8+ T cells balance immunity and tolerance at the maternal-fetal interface.
• Decidual CD8+ T cells are differentiated memory cells with mixed functional states.
• The relationship between antigen specificity and decidual CD8+ T cell function is unclear.
• The presence of unique tissue-resident memory T cells (Trm) versus shared effector memory T cells (Tem) in the decidua is unknown.

Purpose of the Study:

• To characterize the distinct populations of CD8+ T cells in the human decidua.
• To investigate the functional phenotypes of decidual CD8+ T cells based on antigen specificity.
• To determine if decidual CD8+ T cells include unique Trm populations or shared Tem populations.

Main Methods:

• High-dimensional flow cytometry was used to analyze CD8+ T cells from maternal decidua and peripheral blood.
• Decidual and blood CD8+ T cell populations were compared based on their expression of various markers.
• Functional characteristics, including activation, inhibition, and cytotoxicity, were assessed.

Main Results:

• Two Tem populations were identified as shared between blood and decidua.
• Nine distinct Trm clusters, unique to the decidua, were discovered.
• Fetus- and virus-specific decidual CD8+ Trm cells displayed similar profiles of inhibition and cytotoxicity.
• No significant differences were observed in the expression of activation, inhibitory, or cytotoxic molecules between fetus-specific and virus-specific Trm cells.

Conclusions:

• The human decidua harbors unique Trm CD8+ T cell populations distinct from peripheral blood Tem cells.
• Fetal antigen-specific CD8+ Trm cells in the decidua can exhibit cytotoxic and inhibitory functions.
• These findings suggest that not all fetus-specific immune responses are suppressed at the maternal-fetal interface.
• Understanding decidual CD8+ T cell specificity and residency is vital for comprehending placental inflammation and congenital infections.