Human Endothelial Cell Presentation Of Antigen And The Homing Of Memory/Effector T-Cells To Skin
Pober JS, Kluger MS, Schechner JS
Ann N Y Acad Sci. 2001 Sep;941:12-25
Yale University School of Medicine, Department of Dermatology, New Haven, Connecticut 06510, USA
Dermal MicroVascular Endothelial Cells (A HREF="gloss1-g.html#Ependymal">ECs) form a continuous lining that normally bars blood-borne T-Lymphocytes from entering the skin.
But, as part of the response to foreign Antigen, Dermal ECs undergo alterations in their surface proteins so as to provide signals to circulating T-Cells that lead to their activation and recruitment.
Several observations suggest that human Dermal MicroVascular ECs may help initiate cutaneous Immune reactions by presentation of cognate Antigens to circulating T-Memory Cells:
- Antigen-specific inflammatory responses in the skin, as in other organs, involve accumulation of Memory and Effector T-Cell populations that are enriched in cells specific for the eliciting Antigen
- Recall responses to IntraDermal protein Antigens in the skin start very rapidly within two hours of challenge
- Dermal MicroVascular ECs in humans and other large mammals basally display high levels of Class I and Class II MHC molecules, the only known purpose of which is to present AntiGenic Peptides to Lymphocytes
- The Lumen of Dermal Capillaries are narrower than the diameter of circulating T-Cells, ensuring surface contact
- Cultured human ECs effectively present Antigens to resting Memory T-Cells isolated from the circulation
Upon contact with activated T-Cells or their secreted products (Cytokines), Dermal ECs themselves become activated, increasing their capacity to recruit Memory and Effector T-Cell populations in an Antigen-independent manner.
Specifically, activated ECs express inducible Leukocyte Adhesion Molecules such as E-Selectin, ICAM-1, and VCAM-1; and several lines of evidence, including Neutralizing AntiBody experiments and gene knockouts, have supported a role of these molecules in T-Cell recruitment.
Dermal ECs have unique expression patterns of Adhesion Molecules that can determine the subsets of Memory T-Cells that are recruited into the skin.
For example, slow internalization of E-Selectin allows more persistent expression of this protein on the surface of dermal ECs, favoring interactions with CLA-1+ T-Cells.
VCAM-1 expression, normally confined to Venular EC may extend to Capillaries within the Dermal Papillae and contribute to Epidermal inflammation, recruiting alpha4beta7 Integrin-expressing T-Cells that also express the Cadherin-binding Integrin alphaEbeta7.
New models involving transplantation of normal and genetically modified human dermal ECs into ImmunoDeficient mice may be used to further explore these properties.
Growth Factors, Cytokines, Chemokines And NeuroPeptides In The Modeling Of T-Cells
Krueger GR, Marshall GR, Junker U, Schroeder H, Buja LM, Wang G
In Vivo 2002 Sep-Oct;16(5):365-86
University of Texas Houston Medical School, Department of Internal Medicine, Department of Pathology & Laboratory Medicine, 6431 Fannin St., MSB 2.246, Houston, Texas 77030, USA
The T-Lymphocyte lineage, from initial Stem Cells to peripheral mature T-Cells, are members of a highly reactive Cell System engaged in the control of internal homoeostasis and body intactness.
It fulfills its commitments in close communication with the Cellular and Non-Cellular MicroEnvironment and with NeuroEndocrine Regulatory mechanisms.
Tools of such communication are various substances and compounds identified as Cytokines, Chemokines, Hormones, Growth Factors and NeuroPeptides.
Any pathogenetical model of functional aberration and disease development in the T-Cell System must take into account the delicate Network Control exerted by the above mechanisms.
In the following we describe the major players in the network regulation of T-Cell development and function as a basis for a computational modeling study.
Ca2+ Signaling And Membrane Potential In Descending Vasa Recta Pericytes And Endothelia
Rhinehart K, Zhang Z, Pallone TL
Am J Physiol Renal Physiol 2002 Oct;283(4):F852-60
University of Maryland School of Medicine, Division of Nephrology, Baltimore 21201-1595, USA
We devised a method for removal of Pericytes from isolated Descending Vasa Recta (DVR).
After enzymatic digestion, aspiration of a Descending Vas Rectum into a MicroPipette strips the Pericytes from the Abluminal surface. Pericytes and denuded Endothelia can be recovered for separate study.
Using fura 2-loaded preparations, we demonstrated that 10 nM Angiotensin II (ANG II) elevates Pericyte IntraCellular Ca2+ concentration ([Ca2+](i)) and suppresses Endothelial [Ca2+](i).
The Anion transport blocker Probenecid helps retain fura 2 in the Pericyte cytoplasm.
DVR Endothelia were accessed for membrane potential measurement by perforated-patch whole cell recording by using the Pericyte-stripping technique and by turning nondigested vessels inside out with concentric MicroPipettes.
By either method of access, 10 nM ANG II depolarized (n = 20) and 100 nM Bradykinin hyperpolarized (n = 25) the Endothelia.
We conclude that isolated Endothelia and Pericytes remain functional for study of [Ca2+](i) responses and that ANG II and Bradykinin Receptors exist separately on each cell type.
Central Nervous System PeriVascular Cells Are ImmunoRegulatory Cells That Connect The CNS With The Peripheral Immune System
Williams K, Alvarez X, Lackner AA
Glia 2001 Nov;36(2):156-64
Harvard Medical School, Beth Israel Deaconess Medical Center, Division of Viral PathoGenesis, Department of Medicine, Boston, Massachusetts 02215, USA
PeriVascular Cells are a heterogeneous population found in the Central Nervous System (CNS) and the Peripheral Nervous System (PNS).
Several terms are used for these cells, including PeriVascular Cells, PeriVascular Macrophages, PeriVascular Microglia, Fluorescent Granular Perithelial Cells (FGP), or Mato Cells.
Different terminology used may reflect subpopulations of PeriVascular Cells within different anatomic regions and experimental paradigms, NeuroPathological conditions, and species studied.
Different terminology also points to the lack of clear consensus of what cells are PeriVascular Cells in different disease states and models, especially with breakdown of the Blood-Brain Barrier (BBB).
Despite this, there is consensus that PeriVascular Cells, although a minor component of the CNS, are important ImmunoRegulatory Cells. PeriVascular Cells are bone marrow derived, continuously turn over in the CNS, and are found adjacent to CNS vessels.
Thus, they are potential sensors of CNS and Peripheral Immune System perturbations; are activated in models of CNS Inflammation, AutoImmune Disease, Neuronal Injury and Death; and are implicated as Phagocytic and PinoCytotic Cells in models of Stroke and Hypertension.
Recent evidence from our laboratory implicate PeriVascular Cells as primary targets of Human Immunodeficiency Virus (HIV) and Simian Immunodeficiency Virus (SIV) infection in the CNS of humans and macaques.
This article reviews current knowledge of PeriVascular Cells, including anatomic location and nomenclature and putative ImmunoRegulatory roles.
And, discusses new data on the infection of these cells by SIV, their accumulation after SIV infection, and a possible role of the Immune System in SIV Encephalitis.
Copyright 2001 Wiley-Liss, Inc.