4.5 Article

Infection of cattle with Theileria parva induces an early CD8 T cell response lacking appropriate effector function

Journal

INTERNATIONAL JOURNAL FOR PARASITOLOGY
Volume 38, Issue 14, Pages 1693-1704

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.ijpara.2008.05.014

Keywords

Theileria parva; Cattle; CD8 T cell; Pathogenesis; Cytotoxicity; Cytokine; T cell receptor

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Funding

  1. BBSRC
  2. Wellcome Trust [075820]

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Theileria parva causes an acute lympho-proliferative disease in cattle, which can result in death of susceptible animals within 2-3 weeks of infection. Analyses of the cellular response in the lymph node draining the site of infection demonstrated an early T cell response, with the appearance of large numbers of uninfected lymphoblasts between 6 and 9 days p.i., coinciding with initial detection of parasitised cells. There was a marked increase in the representation of CD8(+) T cells and the emergence of a sizable sub-population of CD2(-) CD8(+) alpha/beta T cells during this period. Analysis of T cell receptor beta chain variable (TCR BV) gene expression did not reveal any evidence for the involvement of a superantigen in stimulating the response. Responding lymph node cells were found to produce increased quantities of IFN gamma and IL-10, and both the CD2(+) CD8(+) and CD2(-) CD8(+) populations expressed IFN gamma transcripts. Purified CD2(+) CD8(+) cells proliferated when stimulated in vitro with autologous parasitised cells or non-specific mitogens, whereas CD2(-) CD8(+) cells were refractory to these stimuli. In contrast to the parasite-specific cytotoxic activity associated with T cell responses in immune cattle, the responses to primary infection exhibited variable levels of non-specific cytotoxic activity. Stimulation of purified CD2(+) CD8(+) T cells in vitro with autologous parasitised cells also failed to reveal evidence of specific cytotoxic activity. These findings indicate that primary infection with T parva induces an aberrant T cell response that lacks appropriate effector activity. (C) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

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