Transmaternal cell flow leads to antigen-experienced cord blood

Area of Science:

• Immunology
• Transplantation immunology
• Maternal-fetal medicine

Background:

• Umbilical cord blood (UCB) is a source for hematopoietic stem cell transplantation (HSCT).
• UCB is known to contain antigen-specific T cells.
• The origin of these antigen-specific T cells in UCB, particularly whether they arise from transmaternal cell transfer, is not fully understood.

Purpose of the Study:

• To investigate if transmaternal cell flow can immunize UCB against minor histocompatibility antigens (HY).
• To determine the presence of HY-specific cytotoxic T cells in female UCB.
• To explore the potential role of male microchimerism in maternal circulation and UCB.

Main Methods:

• Analysis of 23 female UCB samples from healthy mothers.
• Isolation and characterization of T-cell clones using tetramer analysis.
• Assessment of male-specific cytotoxic T-cell responses in vitro.
• Detection of male microchimerism in UCB samples.

Main Results:

• Forty-two of 104 T-cell clones from 16 of 17 UCB samples exhibited male-specific lysis.
• Male microchimerism was detected in 6 out of 12 analyzed UCB samples.
• Female UCB contains HY-specific cytotoxic T cells.

Conclusions:

• Female UCB contains HY-specific cytotoxic T cells, indicating prior immunization.
• Transmaternal cell flow of male microchimerism in the mother is the presumed cause of this immunization.
• The presence of non-maternally directed immune cells in UCB may explain improved HSCT outcomes with younger sibling donors.