LIGHT-deficiency impairs CD8+ T cell expansion, but not effector function.
LIGHT, a newly identified member of the tumor necrosis factor (TNF) family, is expressed on activated T lymphocytes. To evaluate how LIGHT contributes to T cell functions, we generated LIGHT-deficient (LIGHT(-/-)) mice using gene targeting. Disruption of LIGHT significantly reduced CD8(+) T cell-cycle progression, leading to reduced proliferation to anti-CD3, anti-CD3/anti-CD28 or allogeneic stimulation, whereas proliferation of CD4(+) T cells remained unchanged. In contrast to the observed proliferative defects, isolated CD8(+) T cells from LIGHT(-/-) mice displayed normal cytotoxic effector function development when compared to wild-type CD8(+) T cells. Underlying a potential mechanism of reduced CD8(+) T cell proliferation, LIGHT(-/-) CD8(+) T cells displayed reduced surface levels of CD25 and a diminished ability to proliferate in response to exogenous IL-2. Furthermore, addition of IL-12 to LIGHT(-/-) CD8(+) T cell cultures could not ameliorate this proliferative defect. These results reveal a potential mechanism of action for LIGHT as a positive regulator of CD8(+) T cell expansion, but not lytic effector function development.
Liu
Jinqi
J
Department of Bio-Research and Technologies and Proteins, Eli Lilly & Co., Indianapolis, IN 46285, USA.
Schmidt
Clint S
CS
Zhao
Feisha
F
Okragly
Angela J
AJ
Glasebrook
Andrew
A
Fox
Niles
N
Galbreath
Elizabeth
E
Zhang
Qing
Q
Song
Ho Yeong
HY
Na
Songqing
S
Yang
Derek D
DD
D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005822:Genetic Vectors; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D007376:Interleukin-2; D008565:Membrane Proteins; D015375:Receptors, Interleukin-2; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12