Experimental allergic encephalomyelitis (EAE), used as an animal model of multiple sclerosis (MS), can be induced by the adoptive transfer of CD4+ T cells that are specific for central nervous system (CNS) antigens While the mechanism(s) responsible for the pathological changes in EAE and MS are not fully defined, the traffic of lymphocytes through the CNS and antigen presentation within the CNS are required events for the development of inflammation Several studies using monoclonal antibodies (mAb) against known molecules expressed on T cells, endothelial cells, or CNS glial cells, have shown that it is possible to inhibit the induction of CNS inflammation in the EAE model In the present study we report a mAb TLD-4A2, obtained by immunizing mice with rat microglia, that recognizes a previously uncharacterized molecule The TLD-4A2 mAb stains resting and activated lymphocytes, as well as activated CNS endothelial cells and microglia The staining pattern of this antibody when screened on tissues from the CNS, lymph node, thymus, and spleen, and by immune- precipitation studies followed by one and two dimension western blots, suggest that it recognizes a novel antigen Treatment of rats with the purified 4A2 mAb resulted in either total inhibition of EAE or a significant delay in its induction and a milder clinical disease TLD-4A2 treatment also resulted in a decreased number T cells and monocyte/macrophages accumulating within perivascular cuffs and penetrating into the CNS parenchyma TLD-4A2 antibody apparently does not directly interfere with T cell function or viability as demonstrated by the ability to recover and stimulate CD4+ encephalitogenic peptide specific T cells from cervical lymph nodes of 4A2 treated animals, and from antibody containing T cell proliferation assays These data suggest that the TLD-4A2 mAb recognizes a novel molecule expressed on lymphocytes, endothelial cells, and macrophages that may play a role in hemato genous cell traffic and the initiation of CNS inflammation

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-40
Application #
6453758
Study Section
Project Start
2001-05-01
Project End
2002-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
40
Fiscal Year
2001
Total Cost
$111,112
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Ma, Qi; Ruan, Hongyu; Peng, Lisheng et al. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A 114:E8760-E8769
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519

Showing the most recent 10 out of 365 publications