Disproportionate Recruitment of CD8 + T Cells into the Central Nervous System by Professional Antigen-Presenting Cells

• Published in: The American journal of pathology Vol. 154; no. 2; pp. 481 - 494
• Main Authors: Carson, Monica J., Reilly, Christina R., Sutcliffe, J. Gregor, Lo, David
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.02.1999; ASIP; American Society for Investigative Pathology
• Subjects: AIDS/HIV; Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Brain - cytology; Brain - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Movement - immunology; Cells, Cultured; Dendritic Cells - immunology; DNA Primers - chemistry; DNA, Complementary - analysis; Flow Cytometry; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myelin Sheath; Neuroglia - cytology; Neurology; Regular; Reverse Transcriptase Polymerase Chain Reaction; RNA - analysis; Autoimmunity; Immunohistochemistry; Multiple sclerosis; Encephalomyelitis; Reverse transcription; Inflammatory disease; T-Lymphocyte; Immunopathology; Dendritic cell; Antigen presentation; Nervous system diseases; Immune response; Rodentia; Cerebral disorder; Polymerase chain reaction; Pathology; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Central nervous system disease; Suppressive cell; Molecular biology; Spinal cord disease
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)65294-7

Inappropriate immune responses, thought to exacerbate or even to initiate several types of central nervous system (CNS) neuropathology, could arise from failures by either the CNS or the immune system. The extent that the inappropriate appearance of antigen-presenting cell (APC) function contributes to CNS inflammation and pathology is still under debate. Therefore, we characterized the response initiated when professional APCs (dendritic cells) presenting non-CNS antigens were injected into the CNS. These dendritic cells expressed numerous T-cell chemokines, but only in the presence of antigen did leukocytes accumulate in the ventricles, meninges, subarachnoid spaces, and injection site. Within the CNS parenchyma, the injected dendritic cells migrated preferentially into the white matter tracts, yet only a small percentage of the recruited leukocytes entered the CNS parenchyma, and then only in the white matter tracts. Although T-cell recruitment was antigen specific and thus mediated by CD4 + T cells in the models used here, CD8 + T cells accumulated in numbers equal to or greater than that of CD4 + T cells. Few of the recruited T cells expressed activation markers (CD25 and VLA-4), and those that did were primarily in the meninges, injection site, ventricles, and perivascular spaces but not in the parenchyma. These results indicate that 1) the CNS modulates the cellular composition and activation states of responding T-cell populations and that 2) myelin-restricted inflammation need not be initiated by a myelin-specific antigen.