Impairment of antigen-presenting cell function by ultraviolet radiation.

Greene, Mark I.; Sy, Man Sun; Kripke, Margaret L.; Benacerraf, Baruj

doi:10.1073/pnas.76.12.6591

Cited by 231 publications

(81 citation statements)

References 22 publications

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“…Previous research indicates that alterations in APC function (5,12) and induction of suppressor T cells (11,14,15) play a critical role in UVmediated immune suppression. In this study, we provide another mechanism by which UV irradiation directly downmodulates T cell immune responses.…”

Section: Discussionmentioning

confidence: 99%

“…Although this phenomenon has been known and studied for Ͼ25 years, the immunologic mechanisms by which tumor tolerance is induced are still not completely understood. Previous studies have shown that UV irradiation may impair the function of APCs (5,12). APCs play a pivotal role in starting Ag-specific immune reactions.…”

Section: Ultraviolet Irradiation Suppresses T Cell Activation Via Blomentioning

confidence: 99%

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Ultraviolet Irradiation Suppresses T Cell Activation via Blocking TCR-Mediated ERK and NF-κB Signaling Pathways

Li‐Weber

Treiber

Giaisi

et al. 2005

The Journal of Immunology

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UV irradiation is carcinogenic and immunosuppressive. Previous studies indicate that UV-mediated alteration of APCs and induction of suppressor T cells play a critical role in UV-induced immune suppression. In this study, we show that UV irradiation can directly (independently of APCs and suppressor T cells) inhibit T cell activation by blocking TCR-mediated phosphorylation of ERK and IκB via overactivation of the p38 and JNK pathways. These events lead to the down-modulation of c-Jun, c-Fos, Egr-1, and NF-κB transcription factors and thereby inhibit production of cytokines, e.g., IL-2, IL-4, IFN-γ, and TNF-α, upon TCR stimulation. We also show that UV irradiation can suppress preactivated T cells, indicating that UV irradiation does not only impair T cell function in response to T cell activation, but can also have systemic effects that influence ongoing immune responses. Thus, our data provide an additional mechanism by which UV irradiation directly suppresses immune responses.

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Section: Discussionmentioning

confidence: 99%

Section: Ultraviolet Irradiation Suppresses T Cell Activation Via Blomentioning

confidence: 99%

Ultraviolet Irradiation Suppresses T Cell Activation via Blocking TCR-Mediated ERK and NF-κB Signaling Pathways

Li‐Weber

Treiber

Giaisi

et al. 2005

The Journal of Immunology

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“…Total body UV exposure also results in a systemic impairment of APC function (7,8). Here again cytokines released in response to UV exposure play an essential role in the systemic alteration of APC function.…”

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confidence: 99%

Exposure to Ultraviolet Radiation Causes Dendritic Cells/Macrophages to Secrete Immune-Suppressive IL-12p40 Homodimers

Schmitt

Ullrich

2000

The Journal of Immunology

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UV-induced immune suppression is a risk factor for sunlight-induced skin cancer. Exposure to UV radiation has been shown to suppress the rejection of highly antigenic UV-induced skin cancers, suppresses delayed and contact hypersensitivity, and depress the ability of dendritic cells to present Ag to T cells. One consequence of UV exposure is altered activation of T cell subsets. APCs from UV-irradiated mice fail to present Ag to Th1 T cells; however, Ag presentation to Th2 T cells is normal. While this has been known for some time, the mechanism behind the preferential suppression of Th1 cell activation has yet to be explained. We tested the hypothesis that this selective impairment of APC function results from altered cytokine production. We found that dendritic cells/macrophages (DC/Mφ) from UV-irradiated mice failed to secrete biologically active IL-12 following in vitro stimulation with LPS. Instead, DC/Mφ isolated from the lymphoid organs of UV-irradiated mice secreted IL-12p40 homodimer, a natural antagonist of biologically active IL-12. Furthermore, when culture supernatants from UV-derived DC/Mφ were added to IL-12-activated T cells, IFN-γ secretion was totally suppressed, indicating that the IL-12p40 homodimer found in the supernatant fluid was biologically active. We suggest that by suppressing DC/Mφ IL-12p70 secretion while promoting IL-12p40 homodimer secretion, UV exposure preferentially suppress the activation of Th1 cells, thereby suppressing Th-1 cell-driven inflammatory immune reactions.

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“…We took advantage of the fact that UV irradiation interferes with the antigen-presenting function of macrophages (22,23). By replacing the second signal with PMA, we demonstrated that induction of the helper T-cell pathway for an alloreactive CTL response requires interaction of macrophages with the antigen before UV irradiation.…”

mentioning

confidence: 99%

Antigen-presenting cell function in induction of helper T cells for cytotoxic T-lymphocyte responses: evidence for antigen processing.

Weinberger¹,

Herrmann²,

Mescher³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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We demonstrate that splenic adherent cells (SACs) play an active role in the presentation of H-2Kk antigen for an alloreactive cytotoxic T-lymphocyte (CTL) response. If antigen is incubated with SACs for 12 hr, they will provide maximal stimulation and present the antigen in the context of their Ia molecules. UV irradiation of these SACs, prior to the 12-hr incubation with H-2Kk antigen, abrogates this stimulatory capacity. Macrophage-bound antigen is not sufficient for stimulation of a response; a second signal is required as well, that, in our system, is provided by phorbol myristic acetate. The SACs are involved in the activation of helper T cells; however, they are not required for presentation of antigen to the precytotoxic T-lymphocyte, which requires two signals for activation, one provided by antigen and the other by a T-cell-derived helper factor. Mononuclear phagocytes are a crucial component of immune responses in humoral (1, 2), proliferative (3, 4), and cytotoxic systems (5-7). Macrophages are required for the uptake and presentation of soluble protein antigens that precedes in vitro T-lymphocyte proliferation and T-and B-lymphocyte collaboration for an antibody response. Further, macrophage-lymphocyte interactions are regulated by the major histocompatibility complex (8-11), specifically, by the Ia molecules on the sensitizing macrophages (12)(13)(14). Macrophage uptake and presentation is not limited to soluble protein antigens; it has recently been shown that radio-resistant splenic adherent cells (SACs) are required for the generation of cytotoxic T-lymphocyte (CTL) responses to both allogeneic membrane proteins (7) and trinitrophenyl-modified cells (6).It is possible to isolate MHC antigens that are serologically active and able to stimulate a CTL response. The H-2Kk antigen can be purified from cell membranes by affinity chromatography with a monoclonal anti-H-2Kk antibody column (15) T-cell responses to mitogens (17, 18) and alloantigens (19) have been described. It has been speculated that such a factor, termed lymphocyte-activating factor (LAF) (17) or interleukin 1 (see ref. 20 for revision to the nomenclature), provides the "second signal" required for T-cell activation. Rosenstreich et al (21) have shown that a synthetic compound, phorbol myristic acetate (PMA), can replace macrophages as a source of this activating signal. The availability of such a reagent is a useful tool for separating the components of macrophage function.In these studies, we examined the nature of the antigen signal provided to the helper T cell. We took advantage of the fact that UV irradiation interferes with the antigen-presenting function of macrophages (22,23). By replacing the second signal with PMA, we demonstrated that induction of the helper T-cell pathway for an alloreactive CTL response requires interaction of macrophages with the antigen before UV irradiation. MATERIALS AND METHODSMice. (BALB/c X DBA/2)F1 (CD2F,) (H-2d) mice [6][7][8][9][10][11][12] weeks of age, were purchased from Cumberland...

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Impairment of antigen-presenting cell function by ultraviolet radiation.

Cited by 231 publications

References 22 publications

Ultraviolet Irradiation Suppresses T Cell Activation via Blocking TCR-Mediated ERK and NF-κB Signaling Pathways

Ultraviolet Irradiation Suppresses T Cell Activation via Blocking TCR-Mediated ERK and NF-κB Signaling Pathways

Exposure to Ultraviolet Radiation Causes Dendritic Cells/Macrophages to Secrete Immune-Suppressive IL-12p40 Homodimers

Antigen-presenting cell function in induction of helper T cells for cytotoxic T-lymphocyte responses: evidence for antigen processing.

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