In vitro correlates of Ld-restricted resistance to toxoplasmic encephalitis and their critical dependence on parasite strain.
Resistance to murine toxoplasmic encephalitis has been precisely and definitively mapped to the L(d) class I gene. Consistent with this, CD8(+) T cells can adoptively transfer resistance to toxoplasmic encephalitis. However, cytotoxic CD8(+) T cells, capable of killing class I-matched, infected target cells, are generated during the course of Toxoplasma gondii infection even in mice lacking the L(d) gene. L(d)-restricted killing could not be demonstrated, and the functional correlate of the L(d) gene has therefore remained elusive. Herein, L(d)-restricted killing of T. gondii-infected target cells is demonstrated for the first time. L(d)-restricted killing is critically dependent on the strain of T. gondii and is observed with all the derivatives of type II strains tested, but not with a type I strain. These results have important implications for vaccine development.
Johnson
Jennifer J
JJ
University of Chicago, Chicago, IL 60637, USA.
Roberts
Craig W
CW
Pope
Constance
C
Roberts
Fiona
F
Kirisits
Michael J
MJ
Estes
Randee
R
Mui
Ernest
E
Krieger
Tim
T
Brown
Charles R
CR
Forman
Jim
J
McLeod
Rima
R
D000818:Animals; D000953:Antigens, Protozoan / Q000494:pharmacology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004660:Encephalitis / Q000235:genetics / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D014774:Virulence
D000953:Antigens, Protozoan; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007371:Interferon-gamma