T cell activation by Theileria annulata-infected macrophages correlates with cytokine production

Abstract

A major feature of the pathology induced by Theileria annulata is acute lymphocytic proliferation, and this study investigates the mechanisms underlying the intrinsic ability of T. annulata-infected monocytes to induce naive autologous T cells to proliferate. Different T. annulata-infected clones expressed different but constant levels of MHC class II, varying from < 1.0 x 105 to 1.5 x 106 molecules/cell, as measured by saturation binding. However, no correlation was found between the level of MHC class II expression and levels of induced T cell proliferation. Theileria annulata-infected cell lines and clones were assayed for cytokine mRNA expression by reverse transcription polymerase chain reaction (RT-PCR). The infected cells assayed produced mRNA specific for IL-1α, IL-1β, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-α), but not IL-2 or IL-4. One clone (clone G) did not produce mRNA for TNF-α. The degree of T cell proliferation induced by infected cells was directly correlated with the amount of mRNA produced for the T cell stimulatory cytokines IL-1α and IL-6, as assessed by a semiquantitative technique. In contrast, cells infected with the related parasite T. parva produced mRNA for IL-1α, IL-2, IL-4, IL-10 and interferon-gamma (IFN-γ). Since T. parva-infected cells also induce naive autologous T cell proliferation, it seems likely that the production of IL-1α by cells infected with either parasite is a major signal for the induction of non-specific T cell proliferation.