Inhibition of lymphocyte proliferation and activation: a mechanism used by equine invasive trophoblast to escape the maternal immune response.

This research investigates how the immune system of a pregnant mare tolerates the presence of invasive foetal cells during pregnancy. The researchers found that these cells, known as trophoblasts, inhibit the growth and activity of certain immune cells possibly contributing to the maternal immune acceptance of the foetus.

Introduction and Background

• The study focuses on a peculiar phenomena occurring in mares during early pregnancy. During this time, so-called invasive trophoblast cells (part of the developing foetus) migrate into the endometrium (the lining of the uterus) no later than the 38th day of gestation. This forms unique structures known as endometrial cups.
• Despite expressing foreign proteins (paternal major histocompatibility complex class I antigens), which should stimulate an immune response, these trophoblast cells remain viable for a significant period post invasion (80-100 days).
• The researchers hypothesised that some sort of immunomodulation must be at play to prevent the mare’s immune system from attacking these foreign cells.

Research Methodology

• An in vitro (outside the body) co-culture system was set up to study the interaction between these invasive trophoblast cells and lymphocytes (a type of immune cell). To control for potential confounding effects, they used fetal fibroblasts from the same foetuses as controls.
• The proliferation (growth and multiplication) and activity of the lymphocytes was observed in the presence of trophoblast cells and their products.

Key Findings

• The presence of invasive trophoblast cells or their pre-conditioned mediums (containing substances secreted by the cells) inhibited the proliferation of the lymphocytes by 50% or more.
• This inhibitory effect required the constant presence of the trophoblast cells or their products and didn’t affect lymphocytes that were already prompted to proliferate.
• All sub-types of lymphocytes were affected in a similar manner.
• Lastly, the expression of certain immune response-associated genes in the lymphocytes (IFNgamma, IL-2, IL-4, and IL-10) was affected compared to controls.

Implications

• The observations suggested that these trophoblast cells have a direct effect on hindering the proliferation and activation of lymphocytes. This could partially explain why the mare’s immune system does not reject the presence of these foetal cells even though they express foreign proteins.
• This immune suppression might extend to other instances where the body needs to tolerate foreign cells, such as in organ transplantation. Future research could explore this possibility.