IL-7 decreases IL-7 receptor alpha (CD127) expression and induces the shedding of CD127 by human CD8+ T cells.
IL-7 receptor alpha (CD127) signaling is essential for T-cell development and regulation of naive and memory T-cell homeostasis. Fewer CD8(+) T cells from HIV-infected patients express CD127 compared with healthy individuals, suggesting that specific host and/or viral factors regulate IL-7 receptor expression. Factors relevant to HIV infection that could potentially decrease CD127 expression on human CD8(+) T cells and the mechanisms by which this occurs were therefore evaluated. IL-7, but not HIV gp120, IL-1-beta, IL-6, IL-10, IL-13, transforming growth factor-beta or tumor necrosis factor-alpha, reduced CD127-surface expression and did so without altering CD127 mRNA expression. Furthermore, IL-7 did not increase the amount of cytoplasmic CD127 in CD8(+) T cells. Interestingly, IL-7 induced the shedding of CD127 from CD8(+) T cells, suggesting a mechanism that may contribute to the increased concentration of CD127 in the plasma of HIV(+) individuals, a novel finding reported here. Naive CD8(+) T cells are more sensitive to IL-7 that mediated the down-regulation of CD127, suggesting that these effects may have particular significance early in T-cell life cycle. Since CD127 down-regulation may be an important contributor to HIV-associated T-cell dysfunction, determining the mechanism thereof may prove to be of considerable significance.
Vranjkovic
Agatha
A
Ottawa Health Research Institute, Ottawa, ON, Canada.
Crawley
Angela M
AM
Gee
Katrina
K
Kumar
Ashok
A
Angel
Jonathan B
JB
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000097:blood / Q000378:metabolism*
D015699:HIV Envelope Protein gp120; D015851:Interleukin-7; D020395:Receptors, Interleukin-7