Parasite‐accessory cell interactions in Theileriosis. Antigen presentation by Theileria annulata‐infected macrophages and production of continuously growing antigen‐presenting cell lines

Abstract

Theileria annulata, a protozoan parasite of cattle, infects major histocompatibility complex (MHC) class II+ cells, particularly macrophages, and transforms them into continuously growing cell lines. We examined the effects of parasitism by T. annulata on antigen-presenting cell function. T. annulata-infected cells (TaH) presented ovalbumin (as measured by [3H]thymidine incorporation) to both resting autologous bovine T cells and ovalbumin-specific bovine CD4+ T cell lines. However, the former cells were also stimulated by TaH without exogenous antigen although to a lesser degree than in the presence of antigen. This "nonspecific" proliferation was not seen with the ovalbumin-specific T cell lines. The magnitude of response by resting T cells in the presence of antigen, to TaH or purified peripheral blood monocytes, was essentially similar. However, on a per cell basis fewer TaH were required. Considerably greater proliferation to antigen was seen with the ovalbumin-specific T cell lines in the presence of TaH compared to monocytes and again fewer TaH were required to elicit a response. The kinetics of processing did not appear to be substantially altered in TaH and the increased proliferation may be due to the elevated MHC class II expression of these cells. Genetic restriction studies with the T cell lines indicated that the restricting elements used to present ovalbumin by TaH were the same as those used by monocytes, as identified by an isoelectric focusing technique. The continuously growing cell lines provide us with a unique model for investigating parasite-accessory cell interactions in theileriosis. The augmented antigen presenting cell activity of TaH may play an important role in the pathogenesis of the disease. TaH will also provide us with a valuable resource for our antigen presentation studies. In particular, the enhanced antigen presentation by TaH enabled us to detect responses to lower levels of antigen, often an important consideration for experiments where the quantity of antigen available is the major limiting factor.

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

“…Our previous studies have shown that T. annulata-'m^ectcd cells have enhanced APC function [4] and also induce aberrant T cell activation and proliferation ; VJ vitro and in vivo [4.5]. Originally we attributed this to the high levels of MHC class 11 expressed on the surface of infected cells [4], Our results here indicate that this is unlikely to be the case.…”

“…Thcileria annuVdia-infected cell line.s and clones A T. amiulaia (Ankara strain)-infected cell line (Theileria anmilala 12929 {T.a 12929)) [8] was established from CDi4p eripheral blood monocytes (PBM) and macrophages of a 6-month-old Friesian calf as previously described [3,4,7]. Clonal ceil lines were produced from this line by soft agar cloning ofthe T.a 12929 cell line generated above [9], Al a eel!…”

“…Proliferation assays T eell proliferation induced by the infected cell lines was measured as previously deseribed [4]. The T. anmilata-infeded cells used in these experiments were passaged 24 h before use; 2 ml of the cell culture were added to 8 ml of fresh medium.…”

“…Infected cells can act as professional anti gen-presenting cells (APC). capable of presenting exogenous antigens to CD4 ^ T cells [4]. However, these cells are also capable of activating naive autoiogous T cells in the absence of exogenous soluble antigen in a contactdependent manner [5].…”

Comparative studies on surface phenotypes of Theileria lestoquardi and T. annulata schizont-infected cells

“…In vitro studies on T. annulata infected cattle lines, using a variety of dierent cell preparations, have demonstrated that upon infection and transformation of the host cells into continuously proliferating schizont-infected cells, alterations in the phenotype of these cells occur Glass et al 1989;Glass and Spooner 1990;Campbell et al 1994;Sager et al 1997Sager et al , 1998a. While cells continue to express the non-lineage speci®c markers CD45, MHC class I and MHC class II, most authors have shown a downregulation of one or more of the monocyte/macrophage lineage markers CD14, CD11b and IL-A24 Spooner et al 1989;Campbell et al 1994;Sager et al 1997).…”