Typically, immune cells are sorted by their morphology and phenotype. However, single-cell analysis technology is changing that up. In this study, researchers at La Jolla Institute for Allergy and Immunology used single-cell transcriptome analysis to study the heterogeneity of CD4 cytotoxic T cells (CTLs) and uncover their origins. The work was published last week and can be found in Science Immunology.
"The observed increase in the ratio of cytotoxic CD4 T cells to CD4 helper T cells indicates that they are an important component of the protective immune response to viral infections and that their induction should be an important marker for successful vaccinations against certain viral diseases," says first author Veena Patil, Ph.D. "But we really didn't know enough about their molecular profile and the mechanisms that drive their differentiation and maintenance."
Using RNA sequencing, Patil analyzed thousands of individual CD4-CTLs isolated from peripheral blood from donors. The analysis revealed the differences between not only individual cells but also within individuals. They report that these CD4-CTLs undergo great clonal expansion. "It is probably the result of the diverse nature of infections and timing of viral exposures coupled with genetic diversity among our study subjects," Patil says.
The team also identified a subset of CD4-CTLs precursors that potentially give rise to fully fledged CD4 CTLs in humans. These precursor cells are characterized by high expression of the interleukin-7 receptor.
"Continually evolving genomic tools and single cell analysis technologies are revolutionizing our understanding of the human immune system in health and disease," says Pandurangan Vijayanand, M.D., Ph.D., who led the study. "But this is just the beginning of the genomic journey. By applying these tools in relevant diseases and cell types we are changing our understanding of the biology of human immune cells."