IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8+ memory T cells.
Generation of CD8(+) memory T cells requires antigenic stimulation through T cell receptor (TCR); however, maintenance of CD8(+) memory T cells seems to be mediated by cytokines, such as IL-15, in a TCR-independent manner. Compared with the TCR-induced activation, less is known about the mechanisms of IL-15 action. We report here a comparative and kinetic analysis of the responses of memory phenotype CD8(+) T cells to IL-15 or TCR (anti-CD3) stimulation in vitro. These two stimuli induce highly similar responses in memory phenotype CD8(+) T cells as measured by cellular proliferation, gene expression changes, synthesis of effector molecules (IFNgamma, tumor necrosis factor beta, granzyme B, and perforin), and induction of cytotoxicity. From 189 genes/expressed sequence tags (ESTs) whose expression changed in CD8(+) memory T cells after IL-15 and anti-CD3 stimulation identified by cDNA microarray analysis, 77% of the genes/ESTs exhibit a highly similar pattern of expression between IL-15 and anti-CD3-treated cells, and only 16% and 7% of the genes/ESTs are differentially expressed in response to IL-15 and anti-CD3 treatments, respectively. These results show that IL-15 and anti-CD3 stimulation induced remarkably similar gene expression and effector function. Thus, IL-15 acts not only as a crucial growth factor but also as an antigen-independent activator of effector functions for CD8(+) memory T cells.
Liu
Kebin
K
Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Catalfamo
Marta
M
Li
Yu
Y
Henkart
Pierre A
PA
Weng
Nan-ping
NP
D015153:Blotting, Western; D017252:CD3 Complex / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D020224:Expressed Sequence Tags; D015894:Genome, Human; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D015854:Up-Regulation
D017252:CD3 Complex; D018076:DNA, Complementary; D019409:Interleukin-15; D011948:Receptors, Antigen, T-Cell