Mothers’ CD4 cells ‘remember’ their babies

By Eleanor McDermid, Senior medwireNews Reporter

A breakthrough in understanding a mother's immune response during pregnancy suggests a new direction for treating autoimmune diseases.

A study of pregnant mice, which appears in Nature, identifies regulatory CD4 cells as those responsible for suppressing maternal immune responses against the developing fetus.

"Knowing this, we can design vaccines that specifically target immune suppressive T cells," said lead researcher Sing Sing Way (University of Minnesota School of Medicine, Minneapolis, USA), in a press statement.

"Current vaccines exclusively target immune activating T cells… A vaccine that targets the expansion and retention of immune suppressive cells would allow selective silencing of undesired responses and prevent them from attacking the body."

Way and team found that CD4 cells with specificity for a fetal antigen (derived from genetically engineered fathers) were significantly upregulated about 10-fold in pregnant mice, and this persisted until about 100 days postpartum. Even mating that did not lead to pregnancy triggered the appearance of these cells, although the response was smaller.

From about mid-term, the CD4 cells became positive for FOXP3, identifying them as regulatory T cells. FOXP3 expression increased as pregnancy progressed.

If the mice fell pregnant a second time, the expansion of regulatory, CD4-positive T cells with fetal antigen specificity was faster than had occurred during the first pregnancy. This shows that the suppressive immune cells were retained from the first pregnancy, "priming" the immune system to deal with subsequent pregnancies.

Virgin mice infected with a bacterium engineered to express the fetal antigen used in the above experiments had a robust T-cell response, as did those that were pregnant but had previously been exposed to the bacterium‑fetal antigen.

But mice not exposed until after pregnancy had no T-cell response, and this hyporesponsiveness was carried through to the postpartum period.

Finally, the team found that mice with second pregnancies were about 60% less likely to lose those pregnancies as a consequence of partial ablation of their T-regulatory cells, relative to mice with first pregnancies.

"These memory features shown in pregnancy illustrate why complications become reduced in subsequent compared with primary pregnancy, but can also be broadly applied to new ways to better control the stringent balance between immune stimulation and suppression for preventing autoimmune diseases," said Way.

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