In vitro correlates of Ld-restricted resistance to toxoplasmic encephalitis and their critical dependence on parasite strain

Jennifer J Johnson, Craig W Roberts, Constance Pope, Fiona Roberts, Michael J Kirisits, Randee Estes, Ernest Mui, Tim Krieger, Charles R Brown, Jim Forman, Rima McLeod

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages966-973
Number of pages8
JournalJournal of Immunology
Volume169
Issue number2
Publication statusPublished - 15 Jul 2002

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Toxoplasma
Encephalitis
Parasites
MHC Class I Genes
T-Lymphocytes
Toxoplasmosis
Genes
Vaccines
In Vitro Techniques

Keywords

  • animals
  • antigens, protozoan
  • cells, cultured
  • cytotoxicity, immunologic
  • encephalitis
  • female
  • H-2 antigens
  • histocompatibility antigen H-2D
  • humans
  • immunity, innate
  • interferon-gamma
  • lymphocyte activation
  • male
  • mice
  • mice, inbred BALB C
  • mice, i`nbred C3H
  • mice, transgenic
  • species specificity
  • spleen
  • T-lymphocytes, cytotoxic
  • toxoplasma
  • toxoplasmosis, animal
  • virulence

Cite this

Johnson, Jennifer J ; Roberts, Craig W ; Pope, Constance ; Roberts, Fiona ; Kirisits, Michael J ; Estes, Randee ; Mui, Ernest ; Krieger, Tim ; Brown, Charles R ; Forman, Jim ; McLeod, Rima. / In vitro correlates of Ld-restricted resistance to toxoplasmic encephalitis and their critical dependence on parasite strain. In: Journal of Immunology. 2002 ; Vol. 169, No. 2. pp. 966-973.
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abstract = "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.",
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Johnson, JJ, Roberts, CW, Pope, C, Roberts, F, Kirisits, MJ, Estes, R, Mui, E, Krieger, T, Brown, CR, Forman, J & McLeod, R 2002, 'In vitro correlates of Ld-restricted resistance to toxoplasmic encephalitis and their critical dependence on parasite strain' Journal of Immunology, vol. 169, no. 2, pp. 966-973.

In vitro correlates of Ld-restricted resistance to toxoplasmic encephalitis and their critical dependence on parasite strain. / Johnson, Jennifer J; Roberts, Craig W; Pope, Constance; Roberts, Fiona; Kirisits, Michael J; Estes, Randee; Mui, Ernest; Krieger, Tim; Brown, Charles R; Forman, Jim; McLeod, Rima.

In: Journal of Immunology, Vol. 169, No. 2, 15.07.2002, p. 966-973.

Research output: Contribution to journalArticle

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AU - Roberts, Craig W

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AU - Roberts, Fiona

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AU - Estes, Randee

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AB - 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.

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KW - mice, transgenic

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