Interleukin-12: Role of Interferon-γ in IL-12 Adverse Effects

1997 ◽  
Vol 83 (1) ◽  
pp. 18-20 ◽  
Author(s):  
Bernhard Ryffel
Keyword(s):  
Adverse Effects ◽  
Interferon Γ ◽  
Interleukin 12

Role of Interferon-γ in Mediating the Antitumor Efficacy of Interleukin-12

1995 ◽  
Vol 17 (2) ◽  
pp. 71-77 ◽  
Author(s):  
Michael J. Brunda ◽  
Leopoldo Luistro ◽  
Jill A. Hendrzak ◽  
Michael Fountoulakis ◽  
Gianni Garotta ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Antitumor Efficacy ◽  
Interleukin 12

scholarly journals TIM-3 blockade enhances IL-12-dependent antitumor immunity by promoting CD8+ T cell and XCR1+ dendritic cell spatial co-localization

2022 ◽  
Vol 10 (1) ◽  
pp. e003571
Author(s):  
Alycia Gardner ◽  
Álvaro de Mingo Pulido ◽  
Kay Hänggi ◽  
Sarah Bazargan ◽  
Alexis Onimus ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interferon Γ ◽  
Response To Therapy ◽  
Interleukin 12 ◽  
Type I ◽  
T Cell Infiltration ◽  
Blocking Antibodies ◽  
Bone Marrow Chimeras

BackgroundT cell immunoglobulin and mucin domain containing−3 (TIM-3) blocking antibodies are currently being evaluated in clinical trials for solid and hematological malignancies. Despite its identification on T cells, TIM-3 is predominantly expressed by myeloid cells, including XCR1+ type I conventional dendritic cells (cDC1s). We have recently shown that TIM-3 blockade promotes expression of CXCR3 chemokine ligands by tumor cDCs, but how this drives a CD8+ T cell-dependent response to therapy is unclear.MethodsT cell infiltration, effector function, and spatial localization in relation to XCR1+ cDC1s were evaluated in a murine orthotopic mammary carcinoma model during response to TIM-3 blockade and paclitaxel chemotherapy. Mixed bone marrow chimeras and diphtheria toxin depletion were used to determine the role of specific genes in cDC1s during therapeutic responses.ResultsTIM-3 blockade increased interferon-γ expression by CD8+ T cells without altering immune infiltration. cDC1 expression of CXCL9, but not CXCL10, was required for response to TIM-3 blockade. CXCL9 was also necessary for the increased proximity observed between CD8+ T cells and XCR1+ cDC1s during therapy. Tumor responses were dependent on cDC1 expression of interleukin-12, but not MHCI.ConclusionsTIM-3 blockade increases exposure of intratumoral CD8+ T cells to cDC1-derived cytokines, with implications for the design of therapeutic strategies using antibodies against TIM-3.

scholarly journals Evidence for the critical role of interleukin-12 but not interferon-γ in the pathogenesis of experimental colitis in mice

2003 ◽  
Vol 18 (5) ◽  
pp. 578-587 ◽  
Author(s):  
KOTARO TOZAWA ◽  
HIROYUKI HANAI ◽  
KEN SUGIMOTO ◽  
SATOSHI BABA ◽  
HARUHIKO SUGIMURA ◽  
...  
Keyword(s):  
Critical Role ◽  
Experimental Colitis ◽  
Interferon Γ ◽  
Interleukin 12

The Essential Role of Interferon-γ During Interleukin-12 Therapy for Murine Transitional Cell Carcinoma of the Bladder

2004 ◽  
Vol 171 (3) ◽  
pp. 1336-1342 ◽  
Author(s):  
MICHAEL A. O’DONNELL ◽  
Y.I. LUO ◽  
SHARON E. HUNTER ◽  
XIAOHONG CHEN ◽  
LORI L. HAYES ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Essential Role ◽  
Transitional Cell ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Carcinoma Of The Bladder

Role of interleukin 12 in hypercholesterolemia-induced inflammation

2003 ◽  
Vol 285 (6) ◽  
pp. H2623-H2629 ◽  
Author(s):  
Karen Y. Stokes ◽  
E. Chris Clanton ◽  
John L. Gehrig ◽  
D. Neil Granger
Keyword(s):  
Stress Responses ◽  
Inflammatory Responses ◽  
Leukocyte Adhesion ◽  
Gene Knockout ◽  
Oxidant Stress ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Leukocyte Adherence ◽  
High Cholesterol

We have previously shown that T lymphocytes and interferon-γ are involved in hypercholesterolemia-induced leukocyte adhesion to vascular endothelium. This study assessed the contribution of interleukin 12 (IL-12) to these hypercholesterolemia-induced inflammatory responses. Intravital videomicroscopy was used to quantify leukocyte adhesion and emigration and oxidant stress (dihydrorhodamine oxidation) in unstimulated cremasteric venules (wall shear rate ≥500 s–1) of wild-type (WT) C57Bl/6, lymphocyte-deficient [recombinase-activating gene knockout (RAG1–/–)], and IL-12-deficient (p35–/– and p40–/–; p35 and p40 are the two subunits of active IL-12) mice on either a normal (ND) or high-cholesterol (HC) diet for 2 wk. RAG1–/–-HC mice received splenocytes from WT-HC (WT → RAG1–/–), p35–/–-HC (p35–/– → RAG1–/–), or p40–/–-HC (p40–/– → RAG1–/–) mice. Compared with WT-ND mice, WT-HC mice exhibited exaggerated leukocyte adherence and emigration as well as increased dihydrorhodamine oxidation. The enhanced leukocyte recruitment was absent in the RAG1–/–-ND, p35–/–-ND, and p40–/–-ND groups. Hypercholesterolemia-induced leukocyte adherence and emigration were attenuated in RAG1–/–-HC vs. WT-HC mice but were similar to ND mice. Furthermore, compared with WT-HC animals, p35–/–-HC and p40–/–-HC mice showed significantly lower leukocyte adhesion and tissue oxidant stress responses, but these values were comparable to ND mice. Leukocyte adherence and emigration in WT → RAG1–/– mice were similar to responses of WT-HC mice. However, p35–/– → RAG1–/– mice had lower levels of adherence and emigration vs. the WT → RAG1–/– and WT-HC groups. Elevated levels of leukocyte adherence and emigration were restored by ∼50% toward WT-HC levels in p40–/– → RAG1–/– mice. These findings implicate IL-12 in the inflammatory responses observed in the venules of hypercholesterolemic mice.

scholarly journals Pivotal Role of Interleukin-12 and Interferon-γ Axis in Controlling Tissue Parasitism and Inflammation in the Heart and Central Nervous System during Trypanosoma cruzi Infection

2001 ◽  
Vol 159 (5) ◽  
pp. 1723-1733 ◽  
Author(s):  
Vladimir Michailowsky ◽  
Neide M. Silva ◽  
Carolina D. Rocha ◽  
Leda Q. Vieira ◽  
Joseli Lannes-Vieira ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Trypanosoma Cruzi ◽  
Interferon Γ ◽  
Pivotal Role ◽  
Interleukin 12 ◽  
Cruzi Infection

scholarly journals Interleukin 12–dependent Interferon γ Production by CD8α+Lymphoid Dendritic Cells

1999 ◽  
Vol 189 (12) ◽  
pp. 1981-1986 ◽  
Author(s):  
Toshiaki Ohteki ◽  
Taro Fukao ◽  
Kazutomo Suzue ◽  
Chikako Maki ◽  
Mamoru Ito ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cell ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Antigen Presenting

We investigated the role of antigen-presenting cells in early interferon (IFN)-γ production in normal and recombinase activating gene 2–deficient (Rag-2−/−) mice in response to Listeria monocytogenes (LM) infection and interleukin (IL)-12 administration. Levels of serum IFN-γ in Rag-2−/− mice were comparable to those of normal mice upon either LM infection or IL-12 injection. Depletion of natural killer (NK) cells by administration of anti-asialoGM1 antibodies had little effect on IFN-γ levels in the sera of Rag-2−/− mice after LM infection or IL-12 injection. Incubation of splenocytes from NK cell–depleted Rag-2−/− mice with LM resulted in the production of IFN-γ that was completely blocked by addition of anti–IL-12 antibodies. Both dendritic cells (DCs) and monocytes purified from splenocytes were capable of producing IFN-γ when cultured in the presence of IL-12. Intracellular immunofluorescence analysis confirmed the IFN-γ production from DCs. It was further shown that IFN-γ was produced predominantly by CD8α+ lymphoid DCs rather than CD8α− myeloid DCs. Collectively, our data indicated that DCs are potent in producing IFN-γ in response to IL-12 produced by bacterial infection and play an important role in innate immunity and subsequent T helper cell type 1 development in vivo.

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