Infection of cattle with Theileria parva induces an early CD8 T cell response lacking appropriate effector function.
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 IFNgamma and IL-10, and both the CD2(+) CD8(+) and CD2(-) CD8(+) populations expressed IFNgamma 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.
Houston
E Fiona
EF
Institute for Animal Health, Compton, Berkshire, RG20 7BH, UK.
Taracha
E L
EL
Brackenbury
Louise
L
MacHugh
N D
ND
McKeever
D J
DJ
Charleston
B
B
Morrison
W I
WI
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002417:Cattle; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D007372:Interferons / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008196:Lymph / Q000276:immunology / Q000469:parasitology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016797:Theileria parva / Q000276:immunology*; D013801:Theileriasis / Q000276:immunology* / Q000473:pathology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D007372:Interferons