Phenotype and regulation of persistent intracerebral T cells in murine Toxoplasma encephalitis.
Toxoplasma gondii is a parasite causing asymptomatic, persistent encephalitis. Protective CD4 and CD8 T cells are recruited to and accumulate in the brain in acute Toxoplasma encephalitis (TE), with slowly decreasing numbers in chronic TE. It is unclear how the size of the intracerebral T cell pool is regulated. Conceivably, permanent recruitment, proliferation, and apoptosis may be involved. We observed that in murine TE recruitment of T cells to the brain was terminated in chronic TE. In vivo 5-bromo-2'-deoxyuridine incorporation and in vitro T cell proliferation experiments revealed that intracerebral T cells did not proliferate, which was explained by the expression of the cell cycle inhibitors p21(Waf/cip1) and p27(Kip1) and the inhibitory activity of intracerebral F4/80(+) cells. TUNEL staining detected apoptotic T cells at low frequency corresponding to an increased expression of the anti-apoptotic molecules Bcl-2 and Bcl-x(L) and a reduced expression of the pro-apoptotic molecules Bad, Bax, and Fas ligand in CD4 and CD8 T cells. During progression from acute to chronic TE, both CD4 and CD8 T cells down-regulated CD45RB expression and expressed a differential pattern of cytokines. From these experiments it is concluded that the number of intracerebral T cells increases by recruitment of T cells during acute infection, whereas proliferation of intracerebral T cells does not play a role. In chronic TE, T cell recruitment is terminated, the phenotype of intracerebral T cells changes, and their number is gradually downsized by low level apoptosis, which, however, does not completely resolve the T cell infiltrates.
Schlüter
Dirk
D
Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Mannheim, Universität Heidelberg, Mannheim, Germany. dirk.schlueter@imh.ma.uni-heidelberg.de
Meyer
Timothy
T
Kwok
Lai-Yu
LY
Montesinos-Rongen
Manuel
M
Lütjen
Sonja
S
Strack
Andreas
A
Schmitz
M Lienhard
ML
Deckert
Martina
M
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001973:Bromodeoxyuridine / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002540:Cerebral Cortex / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D005260:Female; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D013997:Time Factors; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology / Q000473:pathology
D001973:Bromodeoxyuridine