Joint inflammations and exacerbations in mice by cloned helper T cells

textabstractBriefly, the aim of the study described in this thesis was to investigate whether the joint inflammations that occur in AlA can also be induced by cloned helper T cells and the antigen they recognize, and whether these joint inflammations can also show flare-up phenomena after repeated administration of the antigen. In Chapter 2 it is shown that cloned T cells with the helper phenotype can induce delayed type hypersensitivity (DTH) reactions and that these reactions can give rise to flare-up reactions after local, iv or oral administration of the antigen. We hypothesized that these DTH reactions underly the development of joint inflammations in the AlA model, and presumably in human rheumatoid diseases. In Chapter 3 we present the model of induction of joint inflammation by similar cloned T cells. Dose response curves of the antigen and the cloned T cells injected into the joints are shown, as are the kinetics of the joint inflammations induced. Furthermore we show that it is possible to evoke flare-up reactions of these joint inflammations, but also of joint inflammations induced by systemically administered T cells and local injection of the antigen. The induction of joint inflammation by the cloned T cells was found to be dependent on H-2 restricted interactions with recipient cells or tissues. In Chapter 4 we show that both the joint inflammation and the flareup reactions can be evoked in T cell deficient nude mice as well. Furthermore, this paper pays attention to the role of antigen in the retention of the cloned T cells in the joint. In our model, the induction of an inflammatory reaction is dependent on H-2 restricted interactions between T cells and recipient cells and tissues, presumably antigen presenting cells. In Chapter 5 the characterization of a macrophage cell line, AP284, is described that is able to present antigen efficiently in vivo to the cloned helper T cells used in our studies. Injection of AP284 and syngeneic cloned helper T cells into the hind foot of allogeneic mice induces a full blown DTH reaction. This model, in which both the antigen presenting cells and the T cells are monoclonal, is attractive to investigate the cellular interactions in the induction of T cell dependent inflammations. Therefore we applied this approach in our studies on AlA to investigate whether antigen activated helper T cells and macrophages are sufficient for the induction of joint inflammation in allogeneic recipients. The data presented in Chapter 6 show that this was indeed the case. Finally in Chapter 7 we studied in detail the histological and immunohistochemical characteristics of the inflammations and flare-up reactions in our model. The data emerging from our studies are discussed in the perspective of literature data in Chapter