(689) The effect of pregnant serum, cord blood serum and hCG on Jurkat T-cell IL-2 secretion

Type 1 diabetes mellitus (T1DM) results in autoimmune destruction of insulin producing pancreatic beta cells. Although thought to be terminally differentiated, beta cells may undergo expansion during pregnancy. As pregnancy creates a state of immune tolerance, exploring this finding may offer insights to possible therapies for T1DM. We investigated whether circulating factors in serum from pregnant women could reduce the degree of immune activation of human T cells specific for beta cell antigens by measuring interleukin-2 (IL-2). Human chorionic gonadotropin (hCG) is one of the earliest hormones secreted during pregnancy and is known to play a role in immune tolerance. Given this, we investigated hCG’s ability to alter the immune activation in these T cells.

Study Design:

We developed a T cell co culture assay with antigen presenting cells displaying preproinsulin antigen to Jurkat T cells. These Jurkat T cells express a T cell receptor (TCR) specific for preproinsulin peptide presented in the human leukocyte antigen (HLA) Class I serotype HLA-A*02, a globally common HLA allele. The degree of activation of the T cells was measured by the amount IL-2 secreted to the culture media. Human donor sera, cord blood serum and placenta were collected from pregnant women prior to scheduled cesarean delivery. The Jurkat T cell co-culture was treated with various conditions including pregnant serum, cord blood serum, placental extract and extracellular vesicles from each sample.  Following this, The Jurkat T cell co-culture was treated with hCG and IL-2 measured.

Results:

Serum from pregnant women suppresses IL-2 secretion from Jurkat T cells. This indicated a soluble factor in maternal serum and cord blood serum decreases T cell activation. We demonstrated higher concentrations of hCG suppresses IL-2 release.

Conclusion:

Immune tolerance during pregnancy offers a potential role in determining mechanisms to reduce beta cell destruction in T1DM. Human chorionic gonadotrophin hormone reduces human T cell activation targeting beta cell antigens.