Briefly, 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