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Cutting Edge: Emergence of CD127^high Functionally Competent Memory T Cells Is Compromised by High Viral Loads and Inadequate T Cell Help¹

Michael J. Fuller^*, David A. Hildeman, Steffanie Sabbaj, Dalia E. Gaddis^*, Anne E. Tebo^*, Liang Shang^*, Paul A. Goepfert^*, and Allan J. Zajac^2,*

Departments of^* Microbiology and Medicine, University of Alabama, Birmingham, AL 35294; and Division of Immunobiology, Children’s Hospital Medical Center, Cincinnati, OH 45229

In this report we have inspected whether difficulties in controlling viral infections negatively impacts the generation of CD127^high memory T cells. Using both MHC class I and II tetramers we reveal that CD127^low T cells are not necessarily rapidly deleted but can persist in a pseudoeffector state in which they display the hallmarks of activated effector cells but are functionally inferior. CD127^high cells can, however, emerge if the infection is contained. We also show that in the absence of CD4 T cell help significant populations of CD127^high CD8 T cells fail to emerge. Analyses of cytokine-producing activities by both mouse and human CD8 T cells further document that the extended maintenance of T cells in a CD127^low state has functional consequences which manifest as an impairment of IL-2 production.

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