Parasite-mediated steps in immune response failure during primary Theileria annulata infection.

"Exotic" European cattle are highly susceptible to T. annulata infection. In immunised animals, several effective anti-parasite responses can be demonstrated, such as anti-macroschizont cytotoxic T cells (CTL), and nitric oxide killing of parasites. The failure of infected animals to mount an effective primary immune response suggests that the presence of the parasite directly interferes with the development of immunity. When the activation pathways of CD4+ T cells in draining lymph nodes were examined during the course of a primary infection it was found that the development of this essential arm of the immune response was altered. Instead of interacting with antigen presenting cells in the paracortex, the majority of CD4+ T cells were rapidly activated by developing infected cells in the medulla of the node. Activation of T cells by infected cells also drastically alters the cytokines produced by the T cells. During effective immune responses, the principal cytokine involved appears to be IL-2, with only small, controlled "bursts" of IFN gamma production. However, IL-2 responsiveness is only transient in animals undergoing primary infection, while IFNg production is greatly elevated. IFN gamma does not appear to control parasitised cells, and may even aid the growth of infected macrophages--large numbers of macrophages enter the cell cycle during the peak period of IFN gamma production. Uncontrolled parasite-induced IFN gamma production is also likely to account for the local failure of antibody responses. Germinal centres in infected lymph nodes lose normal morphology, with IFN gamma sensitive zones failing to develop. A third strategy which the parasite uses to evade immune response destruction is through affecting CTL activity. CTL in infected draining lymph nodes lose expression of the adhesion molecule CD2--a molecule is essential in adherence to target cells for lysis. CD2- CTL are unable to lyse macroschizont infected cells.