Gamma/delta T cell-deficient mice exhibit reduced disease severity and decreased inflammatory response in the brain in murine neurocysticercosis.
In a recently developed mouse model for neurocysticercosis, the immune response was characterized by a massive influx of gammadelta T cells and a type 1 pathway of cytokine expression. To understand the role of gammadelta T cells during this infection, the cellular and cytokine response was analyzed in mice that lack gammadelta T cells (TCRdelta(-/-)). In TCRdelta(-/-) mice, Mesocestoides corti metacestodes preferentially invaded the extraparenchymal areas of the brain. Furthermore, parasites were able to escape from the brain and establish a systemic infection with liver and peritoneal involvement. Immunopathological studies indicated that TCRdelta(-/-) mice develop little inflammatory response and less neurological symptomatology. Significantly reduced numbers of T cells, macrophages, dendritic cells, and mast cells were present in the brain. The cytokine response in the brain of TCRdelta(-/-) mice appears to be a mixed type1/type 2 response with low levels of IL-2, IL-4, IL-10, IL-12, IL-13, IL-15, and IFN-gamma. To further investigate the immunological significance of this cell population, gammadelta T cells were adoptively transferred into intracranially infected TCRdelta(-/-) mice. gammadelta T cells were specifically recruited into the CNS in response to this parasitic infection, and they were able to target the infected brain within 12 h after transfer. These results suggest that gammadelta T cells are key players in the immune response elicited during this CNS infection and direct a type 1 response in wild-type mice upon infection.
Cardona
Astrid E
AE
Department of Microbiology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Teale
Judy M
JM
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D019676:Genes, T-Cell Receptor delta / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D007970:Leukopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008645:Mesocestoides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020019:Neurocysticercosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta