Issues in T‐helper 1 development – resolved and unresolved

Berenson, Lisa S.; Ota, Naruhisa; Murphy, Kenneth M.

doi:10.1111/j.0105-2896.2004.00208.x

Cited by 86 publications

(63 citation statements)

References 95 publications

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“…Type 1 immune responses and the effector protein IFN-␥ play a critical role in the control of the inflammatory process, the protection against pathogens and tumors (4,5). In this study, we demonstrated that CD47 negatively regulated type 1 humoral and cellular immune responses in vivo.…”

Section: Discussionmentioning

confidence: 55%

“…Nonetheless, IFN-␥ plays a critical role in the protective response against intracellular pathogens that include parasites, mycobacteria, Salmonella, and Listeria (5,10,61). Whether CD47 decreases pathogen-driven Th1 responses remains to be evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…Th1 cells produce mainly IL-2, IFN-␥, TNF-␣, and TNF-␤, elicit delayed-type hypersensitivity responses, and participate in cellular immune responses against intracellular pathogens. Th1 cells are also involved in transplant rejection and protection from neoplasms (5). Th2 cells produce IL-4, IL-5, IL-10, and IL-13, mediate IgG1 and IgE production, eosinophilic inflammation, and are important for elimination of certain extracellular microbes and parasites (6).…”

Section: N Adaptive Immunity Cd4mentioning

confidence: 99%

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CD47 Expression on T Cell Is a Self-Control Negative Regulator of Type 1 Immune Response

Bouguermouh

Van

Martel

et al. 2008

The Journal of Immunology

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The cytokine milieu and dendritic cells (DCs) direct Th1 development. Yet, the control of Th1 polarization by T cell surface molecules remains ill-defined. We here report that CD47 expression on T cells serves as a self-control mechanism to negatively regulate type 1 cellular and humoral immune responses in vivo. Th2-prone BALB/c mice that lack CD47 (CD47−/−) displayed a Th1-biased Ab profile at steady state and after immunization with soluble Ag. CD47−/− mice mounted a T cell-mediated exacerbated and sustained contact hypersensitivity (CHS) response. After their adoptive transfer to naive CD47-deficient hosts 1 day before immunization with soluble Ag, CD47−/− as compared with CD47+/+CD4+ transgenic (Tg) T cells promoted the deviation of Ag-specific T cell responses toward Th1 that were characterized by a high IFN-γ:IL-4 cytokine ratio. Although selective CD47 deficiency on DCs led to increased IL-12p70 production, CD47−/−Tg T cells produced more IFN-γ and displayed higher T-bet expression than CD47+/+ Tg T cells in response to OVA-loaded CD47−/− DCs. CD47 as part of the host environment has no major contribution to the Th1 polarization responses. We thus identify the CD47 molecule as a T cell-negative regulator of type 1 responses that may limit unwanted collateral damage to maximize protection and minimize host injury.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: N Adaptive Immunity Cd4mentioning

confidence: 99%

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CD47 Expression on T Cell Is a Self-Control Negative Regulator of Type 1 Immune Response

Bouguermouh

Van

Martel

et al. 2008

The Journal of Immunology

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“…More recently, it has become clear that IL-12 and IL-18 can also activate T cells in an antigenindependent fashion. 60 Studies of IFN-␥ production by murine CD4 ϩ T cells have characterized separate IL-12/IL-18 and T-cell receptor signaling pathways. 61 Interactions between innate and adaptive stimuli for cytokine responses by murine CD8 ϩ T cells have been investigated in a viral infection model in which both IL-12/IL-18 and antigen result in IFN-␥ production, but only T-cell receptor signaling induces IL-2 secretion, which is pivotal for T-cell clonal expansion.…”

Section: Ccr7mentioning

confidence: 99%

Interferon-γ Axis in Graft Arteriosclerosis

Tellides

Pober

2007

Circulation Research

104

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Abstract-Cardiac transplantation is the most effective treatment for advanced heart failure. Despite improvements in immunosuppression therapy that prevent acute rejection, cardiac allografts fail at rates of 3% to 5% per posttransplant year. The hallmark morphological lesion of chronically failing cardiac allografts, also seen in chronic renal and liver graft failure, is luminal stenosis of blood vessels, especially of conduit arteries. Late graft failure results from widespread secondary ischemic injury to the graft parenchyma rather than direct immune-mediated damage. Although this process affects the entire graft vasculature, graft arteriosclerosis is a suitable term to describe the problem because it applies to different types of failing organs and because it emphasizes the central feature, namely an accelerated form of arterial injury and remodeling. The precise pathogenesis of graft arteriosclerosis is unknown. In this review, we make the case that the signature T-helper type 1 cytokine, interferon (IFN)-␥, is a key effector in graft arteriosclerosis, which, together with the IFN-␥-inducing cytokine interleukin-12 and IFN-␥-inducible chemokines such as CXCR3 ligands, constitute a positive feedback loop for T-cell activation, differentiation, and recruitment that we refer to as the IFN-␥ axis. We evaluate the evidence to support this hypothesis in clinical observational and experimental animal studies. Additionally, we examine the regulation of IFN-␥ production within the artery wall, the effects of IFN-␥ on vessel wall cells, and the outcome of therapeutic agents on IFN-␥ production and signaling. These observations lead us to suggest that new therapies for graft arteriosclerosis should be optimized which focus on reducing IFN-␥ synthesis or actions. (Circ Res. 2007;100:622-632.)

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“…In contrast, STAT-4 was exclusively activated by R5 gp120. STAT-4 is a member of the STAT family of transcription factors and plays a central role in the polarization of T lymphocytes toward a Th1 phenotype (32). (13,14).…”

Section: Figmentioning

confidence: 99%

R5 and X4 HIV envelopes induce distinct gene expression profiles in primary peripheral blood mononuclear cells

Cicala

Arthos²,

Martinelli³

et al. 2006

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

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HIV envelope binds to and signals through its primary cellular receptor, CD4, and through a coreceptor, either CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4). Here, we evaluate the response of peripheral blood mononuclear cells to a panel of genetically diverse R5 and X4 envelope proteins. Modulation of gene expression was evaluated by using oligonucleotide microarrays. Activation of transcription factors was evaluated by using an array of oligonucleotides encoding transcription factor binding sites. Responses were strongly influenced by coreceptor specificity. Treatment of cells from CCR5⌬32 homozygous donors with glycoprotein (gp)120 derived from an R5 virus demonstrated that the majority of responses elicited by R5 envelopes required engagement of CCR5. R5 envelopes, to a greater extent than X4 envelopes, induced the expression of genes belonging to mitogenactivated protein kinase signal transduction pathways and genes regulating the cell cycle. A number of genes induced by R5, but not X4, envelopes were also up-regulated in the resting CD4 ؉ T cell population of HIV-infected individuals. These results suggest that R5 envelope facilitates replication of HIV in the pool of resting CD4 ؉ T cells. Additionally, signaling by R5 gp120 may facilitate the transmission of R5 viruses by inducing a permissive environment for HIV replication.ϩ T cells begins with the fusion of the viral envelope with the outer membrane of a target cell. Fusion is initiated when the viral envelope glycoprotein (gp)120 binds first to CD4 and then to a coreceptor, primarily CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4) (1-4). These interactions between gp120 and cell-surface receptors transduce signals in the target cell. Ligation of CD4 by gp120 increases the tyrosine kinase activity of p56lck, a src-related protein kinase associated with the cytoplasmic domain of CD4 on CD4 ϩ T cell membranes (5). Engagement of CCR5 and CXCR4 by gp120 also mediates signaling events (6-9), as evidenced by the rapid mobilization of Ca ϩϩ , and the phosphorylation of intracellular substrates including PYK2 and FAK (10,11). In this respect, the HIV envelope protein delivers a unique near simultaneous dual signal to CD4 ϩ T cells. No protein in the human proteome has been shown to deliver an analogous signal. The response to this stimulus depends on the state of differentiation and activation of the targeted cell. A number of reports demonstrate that envelope induces activated CD4 ϩ T cells to apoptose in vitro (12-15). Envelope proteins have also been shown to disrupt antigen-specific CD4 ϩ T cell responses (16). We have focused on the impact of envelope-mediated signaling on resting CD4 ϩ T cells. These cells constitute one of the latent reservoirs of HIV that prevents eradication of virus from infected individuals, even after prolonged treatment with potent antiretroviral drugs (17,18). In vitro exposure of resting CD4 ϩ T cells derived from HIV-infected individuals to envelope results in a burst of viral replicatio...

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Issues in T‐helper 1 development – resolved and unresolved

Cited by 86 publications

References 95 publications

CD47 Expression on T Cell Is a Self-Control Negative Regulator of Type 1 Immune Response

CD47 Expression on T Cell Is a Self-Control Negative Regulator of Type 1 Immune Response

Interferon-γ Axis in Graft Arteriosclerosis

R5 and X4 HIV envelopes induce distinct gene expression profiles in primary peripheral blood mononuclear cells

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