Mj. Carson et al., Disproportionate recruitment of CD8(+) T cells into the central nervous system by professional antigen-presenting cells, AM J PATH, 154(2), 1999, pp. 481-494
Citations number
44
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Inappropriate immune responses, thought to exacerbate or even to initiate s
everal types of central nervous system (CNS) neuropathology, could arise fr
om failures by either the CNS or the immune system. The extent that the ina
ppropriate appearance of antigen-presenting cell (APC) function contributes
to CNS inflammation and pathology is still under debate. Therefore, we cha
racterized the response initiated when professional APCs (dendritic cells)
presenting non-CNS antigens were injected into the CNS, These dendritic cel
ls expressed numerous T-cell chemokines, but only in the presence of antige
n did leukocytes accumulate in the ventricles, meninges, subarachnoid space
s, and injection site. Within the CNS parenchyma, the injected dendritic ce
lls 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 s
pecific 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 c
ells. Few of the recruited T cells expressed activation markers (CD25 and V
LA-4), and those that did were primarily in the meninges, injection site, v
entricles, 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 infl
ammation need not be initiated by a myelin-specific antigen.