Fragile privileges: autoimmunity in brain and eye

Wekerle, Hartmut; Sun, Deming

doi:10.1038/aps.2010.149

Cited by 12 publications

(9 citation statements)

References 37 publications

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“…The eye, similar to the brain, possesses a blood-ocular barrier that generally limits immune activation in the ocular tissues [20–22]. Whether HIV infection of the eye mirrors that of the brain, with genetically distinct HIV variants that utilize the CCR5 co-receptor and forms a distinct viral compartment from the blood [22], or whether viruses in the eye are in perpetual interchange with variants in the blood, has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

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Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals

Williams-Wietzikoski

Bull

et al. 2017

Aids

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OBJECTIVE To analyze and compare human immunodeficiency virus type-1 (HIV) env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease. DESIGN A prospective case series of five HIV-infected antiretroviral (ARV)-naïve individuals with uveitis negative for other pathogens. METHODS RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers. HIV env C2–V5 (HXB2: 6990–7668) sequences were generated by single-genome-amplification (SGA) using nested polymerase-chain-reaction (PCR) followed by bi-directional Sanger sequencing. Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy evaluated relationships between HIV in plasma and aqueous humor. RESULTS A median of 20 (range: 13–22) plasma and 15 (range: 9–18) aqueous humor sequences were generated from each individual. The frequencies of sequences with predicted-N-linked-glycosylation-sites (PNLGS) and C-X-C chemokine receptor type 4 (CXCR4) were comparable in aqueous humor and plasma of all five subjects. Aqueous humor sequences had lower median genetic diversity compared to plasma across all subjects, but similar divergence, in 4 of 5 subjects. Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index. CONCLUSIONS Among ARV-naïve individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared to blood sequences suggests time-limited passage of a small subset of variants from each subject’s viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.

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Section: Discussionmentioning

confidence: 99%

“…The uvea within the eye, is an immune privileged site similar to central nervous system and possesses a blood-ocular barrier analogous to brain-blood barrier [20–22]. Previous studies have shown that HIV could be recovered from multiple ocular tissues, such as the retina, conjunctiva, cornea, and iris of patients with AIDS [23, 24].…”

Section: Introductionmentioning

confidence: 99%

Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals

Williams-Wietzikoski

Bull

et al. 2017

Aids

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“…The retina is a part of the central nervous system and consequently is an immune privileged tissue [ 16 , 59 ]. Ocular immune privilege is physiologically maintained by the blood/retina barrier, but microglia also modulates the process by secretion of pro- or anti-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients

Gramlich

Ding

Zhu

et al. 2015

acta neuropathol commun

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IntroductionSeveral studies have indicated that autoimmune and neuroinflammatory processes contribute to the neurodegeneration of retinal ganglion cells in human glaucoma patients and in animal models. To test the involvement of cellular immune processes in the pathophysiology of retinal ganglion cell degeneration in vivo, we carried out adoptive transfer experiments from two independent genetic mouse models of glaucoma into normal recipient mice.ResultsOur findings indicate that transfer results in a progressive loss of retinal ganglion cells and their axons despite normal intraocular pressure in recipient mice. Signs of pan-retinal inflammation were not detected. Similar findings were obtained following transfer of isolated T-lymphocytes, but not after transfer of splenocytes from immune deficient glaucomatous mice. Transferred lymphocytes were detected integrated in the spleen and in the retinal ganglion cell layer of recipient animals, albeit at very low frequencies. Furthermore, we observed cell-cell interaction between transferred T-cells and recipient microglia along with focal microglial activation in recipient eyes.ConclusionThis study demonstrates that the pathophysiology of glaucomatous degeneration in the tested animal models includes T-cell mediated events that are capable of causing loss of healthy retinal ganglion cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0234-y) contains supplementary material, which is available to authorized users.

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“…Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS), where immune cells specific to CNS antigens damage the CNS, resulting in paralysis [64][65][66][67][68][69][70][71][72][73]. Autoimmune T cells traffic to the brain and cross the BBB and causes damage [74], thus preventing T cell migration to the CNS is a therapeutic target.…”

Section: Potential Role Of Cns Lymphatics In Health and Diseasementioning

confidence: 99%

Revisiting the Mechanisms of CNS Immune Privilege

Louveau

Harris

Kipnis

2015

Trends in Immunology

536

399

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Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders.

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Fragile privileges: autoimmunity in brain and eye

Cited by 12 publications

References 37 publications

Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals

Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals

Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients

Revisiting the Mechanisms of CNS Immune Privilege

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