Regulation and Function of Class II Major Histocompatibility Complex, CD40, and B7 Expression in Macrophages and Microglia: Implications in Neurological Diseases

O'Keefe, George M; Nguyen, Vince T.; Benveniste, Etty N.

doi:10.1080/13550280290100941

Cited by 85 publications

(63 citation statements)

References 163 publications

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“…MHC II ϩ microglial cells have been shown to be an important element in host resistance to cerebral cryptococcosis (21). Activated microglial cells have been demonstrated to engulf C. neoformans and function as APCs by up-regulating MHC class II expression as well as other costimulatory molecules such as CD80, CD86, and CD40 (47) through which they are able to interact with T cells and gain enhanced microbial resistance (47)(48)(49). Therefore, the marked up-regulation of MHC class II expression on microglial cells induced by anti-CD40 and IL-2 treatment in this study indicated that these cells were activated.…”

Section: Discussionmentioning

confidence: 99%

Protection from Direct Cerebral Cryptococcus Infection by Interferon-γ-Dependent Activation of Microglial Cells

Zhou

Gault

Kozel

et al. 2007

The Journal of Immunology

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The brain represents a significant barrier for protective immune responses in both infectious disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-γ knockout mice and IFN-γR knockout mice demonstrated that IFN-γ was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-γ production and microglial cell activation were observed early after treatment, negligible IFN-γ was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-γ is essential for this effect.

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Section: Discussionmentioning

confidence: 99%

Protection from Direct Cerebral Cryptococcus Infection by Interferon-γ-Dependent Activation of Microglial Cells

Zhou

Gault

Kozel

et al. 2007

The Journal of Immunology

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“…For instance, some latent viruses such as JC virus or varicella zoster produce clinical syndromes mainly in immuno-compromised individuals. MHC and co-stimulatory molecules are strongly increased in CNS infection and a number of CNS pathologic conditions, including ischemia, neoplasm, traumatic nerve injury and neurodegenerative diseases such as AD, PD, MS, HIV-dementia and Creutzfeldt-Jacob disease (Maehlen et al, 1989;McGeer et al, 1993;Graeber et al, 1998;Perry, 1998;Dorries, 2001;Piehl and Lidman, 2001;O'Keefe et al, 2002;Owens, 2002). Recent evidence has implied that the CNS equips itself with a unique defense system with its own molecular and cellular components despite sharing certain properties with the peripheral immune system.…”

Section: Unique Immune Properties Of the Central Nervous Systemmentioning

confidence: 99%

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

Kim

Joh²

2006

Exp Mol Med

594

450

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Inflammation, a self-defensive reaction against various pathogenic stimuli, may become harmful self-damaging process. Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central nervous system, microglia, the resident innate immune cells play major role in the inflammatory process. Although they form the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines (IL-1β, TNF-α, IL-6), NO, PGE2, and superoxide. Moreover, our recent study demonstrated that activated microglia phagocytose not only damaged cell debris but also neighboring intact cells. It further supports their active participation in self-perpetuating neuronal damaging cycles. In the following review, we discuss microglial responses to damaging neurons, known activators released from injured neurons and how microglia cause neuronal degeneration. In the last part, microglial activation and their role in PD are discussed in depth.

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“…7 Once neuronal damage occurs, T cells and antigen-presenting cells (APC) accumulate at lesion sites, with concomitant increased expression of the major histocompatibility complex (MHC) and costimulatory molecules, which are necessary for T-cell activation. [8][9][10][11] It is perceivable that a strict control of the activation of T cells is important to ameliorate their harmful effects on neurons.Optimal activation of T cells by APCs requires at least 2 signals. The first is elicited through recognition of the MHC-peptide complex by T-cell receptor (TCR), and the second is provided by the costimulatory molecules via interaction with their respective receptors on T cells.…”

mentioning

confidence: 99%

Shedded neuronal ICAM-5 suppresses T-cell activation

Tian

Lappalainen

Autero

et al. 2008

Blood

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IntroductionInflammation is generally regarded as harmful to the brain because local and infiltrated immune cells, as well as proinflammatory cytokines, exacerbate the neuronal damage in various neurodegenerative and autoimmune diseases. 1-4 Healthy brain prevents the penetration of lymphocytes into the brain parenchyma and also down-regulates the activity of infiltrated lymphocytes. 5,6 Nevertheless, the brain is neither isolated nor passive in its interactions with the immune system. 7 Once neuronal damage occurs, T cells and antigen-presenting cells (APC) accumulate at lesion sites, with concomitant increased expression of the major histocompatibility complex (MHC) and costimulatory molecules, which are necessary for T-cell activation. [8][9][10][11] It is perceivable that a strict control of the activation of T cells is important to ameliorate their harmful effects on neurons.Optimal activation of T cells by APCs requires at least 2 signals. The first is elicited through recognition of the MHC-peptide complex by T-cell receptor (TCR), and the second is provided by the costimulatory molecules via interaction with their respective receptors on T cells. Costimulatory molecules are key factors required for full activation of the primed T cells, especially the naive T cells. Without costimulation, the primed T cells will turn into unresponsiveness or anergy. [12][13][14] Among the costimulatory molecules, B7 (CD80 or 86), CD40, and intercellular adhesion molecule (ICAM)-1 have all been detected at inflammatory sites in brain. 8,10,11 ICAM-1 is known to promote the activation of T cells through binding to its integrin receptor lymphocyte function associated antigen-1 (LFA-1, ␣L␤2, CD11a/CD18). 15-17 LFA-1 and ICAM-1 are involved in the formation of the adhesion ring junction or the peripheral supramolecular activation complex at the immunologic synapse between T cells and APCs. 18,19 The ICAMs belong to the immunoglobulin (Ig) superfamily, and 5 ICAM members (ICAM-1-5) have been identified. 20,21 In brain, ICAM-1 is expressed in endothelial, epithelial, and glial cells. 22 By contrast, ICAM-5 (telencephalin) has been shown to be expressed only in the telencephalic neurons, and its synthesis takes place mainly after birth. 23 Structurally, ICAM-5 is a type I membrane protein with 9 Ig-like domains in the extracellular part, a short transmembrane region, and a cytoplasmic tail. 23,24 ICAM-5 has been shown to bind to LFA-1 [25][26][27] and to regulate the morphology of microglia. 28 In conditions of brain ischemia, 29 epilepsy, 30,31 and encephalitis, 32 the soluble form of ICAM-5 (sICAM-5) has been detected in physiologic fluids.Because of its specific expression pattern, and also being a ligand for LFA-1, it is crucial to establish whether ICAM-5 can act as a costimulatory molecule for T cells, as ICAM-1 does, and whether it regulates T-cell activity during brain inflammation. Here, we find that, in contrast to ICAM-1, the expression of ICAM-5 is not up-regulated by the cytokines tumor necrosis factor (TNF) and int...

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Regulation and Function of Class II Major Histocompatibility Complex, CD40, and B7 Expression in Macrophages and Microglia: Implications in Neurological Diseases

Cited by 85 publications

References 163 publications

Protection from Direct Cerebral Cryptococcus Infection by Interferon-γ-Dependent Activation of Microglial Cells

Protection from Direct Cerebral Cryptococcus Infection by Interferon-γ-Dependent Activation of Microglial Cells

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

Shedded neuronal ICAM-5 suppresses T-cell activation

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