IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner.
The CD31(+) subset of human naive CD4(+) T cells is thought to contain the population of cells that have recently emigrated from the thymus, while their CD31(-) counterparts have been proposed to originate from CD31(+) cells after homeostatic cell division. Naive T-cell maintenance is known to involve homeostatic cytokines such as interleukin-7 (IL-7). It remains to be investigated what role this cytokine has in the homeostasis of naive CD4(+) T-cell subsets defined by CD31 expression. We provide evidence that IL-7 exerts a preferential proliferative effect on CD31(+) naive CD4(+) T cells from adult peripheral blood compared with the CD31(-) subset. IL-7-driven proliferation did not result in loss of CD31 expression, suggesting that CD31(+) naive CD4(+) T cells can undergo cytokine-driven homeostatic proliferation while preserving CD31. Furthermore, IL-7 sustained or increased CD31 expression even in nonproliferating cells. Both proliferation and CD31 maintenance were dependent on the activation of phosphoinositide 3-kinase (PI3K) signaling. Taken together, our data suggest that during adulthood CD31(+) naive CD4(+) T cells are maintained by IL-7 and that IL-7-based therapies may exert a preferential effect on this population.
Azevedo
Rita I
RI
Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Soares
Maria Vieira D
MV
Barata
João T
JT
Tendeiro
Rita
R
Serra-Caetano
Ana
A
Victorino
Rui M M
RM
Sousa
Ana E
AE
D000328:Adult; D000375:Aging / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D015851:Interleukin-7 / Q000494:pharmacology* / Q000502:physiology; D009928:Organ Specificity / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D015851:Interleukin-7; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases