Typically, human immune cells are split into two groups, innate and adaptive. Innate cells act as the body’s first line of defense, reacting nonspecifically to infections and other threats. Adaptive cells provide long-term memory and immunity to specific infectious agents, but these cells take time to learn what is a threat. The virtual memory T cells did not fit into either group.
“We found that these virtual memory T cells had hallmarks of both innate and adaptive immunity,” said first author Anoop Babu Vasandan, PhD, St. Jude Department of Immunology. “These cells existed somewhere in the middle between them.”
The researchers discovered that these cells had epigenetic and protein markers of both innate and adaptive cells. In functional tests, they reacted nonspecifically to immune signals of infectious threats, an innate-like reaction, while delivering an adaptive molecule, interferon-gamma, to neutralize them. These T cells’ existence between the two categories possibly provides a connection between fast-acting innate and long-lasting adaptive immunity before early immune memory forms.
“These virtual memory T cells are likely acting as a bridge until infants are out in the world and experiencing different infectious threats that educate their immune system,” said co-corresponding author Caitlin Zebley, MD, PhD, St. Department of Bone Marrow Transplantation & Cellular Therapy. “They allow the adaptive immune system time to undergo those first educational processes and develop true, rather than ‘virtual’ memory.”
While the study is the first to characterize these cells in early human immune development, much remains a mystery about this difficult-to-study cell type.
“Now we need to find ways to continue to study these virtual memory T cells and see if we can use them to improve childhood vaccinations or adapt them for other uses, such as immunotherapy,” Youngblood said. “We’ve only scratched the surface of understanding their potential.”
Reference: Vasandan AB, Abdelsamed HA, Boi SK, et al. Innate-like memory T cells rapidly emerge in humans after gene therapy for SCID-X1 test. Immunity. doi: 10.1016/j.immuni.2025.07.002
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