Men and women do have immune cell differences, study says

T cells play a crucial function in fighting infections and malignancies, but they can also perform a role in the development of autoimmune illnesses. Researchers at the La Jolla Institute for Immunology (LJI) have uncovered novel genes associated with the risk of autoimmune disorders in the CD4+ “helper” T cell subset.

Image Credit: La Jolla Institute for Immunology.

The researchers have discovered big disparities between donors depending on genetics and how the cells may behave in men and women as they try to understand the exact activities of these CD4+ T cell subsets.

The LJI team has developed a free online resource for other immunologists across the world who wants to explore the data sets in real-time, save, and use their data to support future studies into human immunity. This data is part of the Database of Immune Cell Gene Expression, Expression Quantitative Trait Loci (eQTLs), and Epigenomics (DICE), which is hosted by the LJI.

“This investigation expands our DICE resource to help scientists find target genes and cell types linked to risk of human diseases,” says study leader and LJI Professor Pandurangan Vijayanand, MD, PhD.

Vijayanand was also a member of the LJI Center for Autoimmunity and Inflammation and Center for Cancer Immunotherapy.

These cells are critical for protecting the body, and we uncovered many new genes that are linked to risk of human diseases.”

Benjamin Schmiedel PhD, Study First Author and Instructor, La Jolla Institute for Immunology

The new study gives scientists the most detailed and comprehensive look yet at gene expression differences amongst CD4+ T cell subsets. The researchers examined gene expression changes in over a million CD4+ T cells from 89 healthy blood donors using a technique called single-cell RNA sequencing. The study was published in the journal Science Immunology.

The LJI scientists expected to uncover significant differences in cell subsets because T cells can play a variety of tasks in the body, including “remembering” past invaders and notifying other immune cells. In fact, researchers went out with the goal of learning more about eight pre-defined CD4+ T cell subgroups that they had looked into in a 2018 Cell research.

Researchers looked at distinct T cell subsets extracted from blood samples without activating them in prior experiments. Before sequencing and analysis, the LJI team stimulated the T cells for this new investigation. The researchers were able to simulate how the cells would react if they were called upon to perform their function and defend the body from infection by taking this step.

Stimulating the cells is like turning on the light—suddenly you can understand the function of these cells much better.”

Benjamin Schmiedel PhD, Study First Author and Instructor, La Jolla Institute for Immunology

This research illuminated previously unknown cell subsets while also revealing new, little-understood subsets.

Why do these cells have different features? There is no information in the literature to help us understand what those cells are, so that’s something we want to follow up on.”

Benjamin Schmiedel PhD, Study First Author and Instructor, La Jolla Institute for Immunology

Using single-cell expression quantitative trait loci (sc-Eqtl) analysis, the scientists have already learned more about these T cells. This method revealed which genes are influenced by heredity and which have the greatest impact across T cell subtypes.

The researchers also discovered significant sex-based variations in how T cells functioned. The researchers noted differences in how the various CD4+ T cell subsets interact with other immune cells and create disease-fighting cytokines when they compared the cells of persons who were born male or female. Biological sex is demonstrated to play a crucial role in how these cells function.

These distinctions may explain why men are more susceptible to viral diseases like COVID-19 and why women are more susceptible to autoimmune diseases.

“If we can understand how an immune cell from a woman differs from an immune cell from a man, we could figure out why certain diseases affect one sex more often than another,” says Schmiedel.