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Researchers have described the earliest stages of fate determination among white blood cells called T lymphocytes, providing new insights that may help drug developers create more effective, longer-lasting vaccines against microbial pathogens or cancer.

Naive T lymphocytes patrol the front lines of the human body's defense against infection, circulating in blood and tissues, searching for invasive microbes and other foreign antigens.

They're called "naive" because they have not yet encountered an invader. When they do, these T cells activate and divide, giving rise to two types of daughter cells: "effector lymphocytes" responsible for immediate host defense and "memory lymphocytes" that provide long-term protection from similar infections.

John T. Chang, MD, assistant professor in the Department of Medicine and the study's co-principal investigator, along with Gene W. Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine and Institute for Genomic Medicine, said that researchers have been trying for a very long time to understand when and how T lymphocytes give rise to effector and memory cells during an infection.

First authors Janilyn Arsenio, a postdoctoral fellow in the Chang lab and Boyko Kakaradov, a graduate student in the Yeo lab and UCSD Bioinformatics graduate program said that they took advantage of recent technological advances in single-cell gene expression profiling and cutting-edge machine-learning algorithms to address this question on a level of detail that was not previously possible.

Chang, Yeo and colleagues discovered that the decision by an individual T cell to produce effector and memory cells is made almost at the moment of infection. "The 'mother' lymphocyte seems to divide into two daughter cells that are already different from birth," said Chang, "with one becoming an effector cell while its sister becomes a memory cell."

The findings have been published online in the journal Nature Immunology.