Tissue Damage and Type 1 T Cells

Type 1 T cells are associated with two distinct types of tissue damage. One type of tissue damage is characterized by a sterile inflammation, the other with the strong accumulation of polymorphonuclear granulocytes.

Sterile type 1 responses are found in lichen planus, multiple sclerosis or autoimmune diabetes. They are associated with activated macrophages, which seem to be the effector cells of these immune responses. Like macrophages that are stimulated in vitro in the presence of IFNy, they produce large amounts of TNF, oxygen radicals, NO and other mediators of inflammation (Stenger and Modlin 1999). Activated CD8+ T cells with potent killer functions seem also to be involved (Zinkernagel 1996). In concert, these mediators can cause severe tissue destruction that ultimately results in compensatory scar formation. Due to the capacity of the skin to regenerate even severe tissue damage, lichen planus heals under most conditions without scaring. However, persistent alopecia, onychodystrophy or even scars of the normal skin are potential complications (Fig. 5A).

Under other conditions, type 1 mediated autoimmune diseases are associated with a strong infiltrate by PMN. Such a constellation characterizes psoriasis,

Fig. 5. Different types of inflammation induced by either IFNy-producing Th1 and by IL-4-producing Th2 cells

rheumatiod arthritis (RA) and most types of inflammatory bowel disease, especially Crohn's disease (Mican and Metcalfe 1990; Rothe et al. 1990; Strober and Ehrhardt 1993; Christophers 1996; Feldmann et al. 1996; Ackermann and Harvima 1998; Bischoff et al. 1999; Gelbmann et al. 1999; Biedermann et al. 2000). Numerous reports describe that PMN recruitment is closely associated with accumulation of IL-8, TNF and the presence of activated mast cells. Studies in an animal model of skin inflammation unraveled important mechanisms leading to strong PMN recruitment during type 1 immune responses. In a mouse model of type 1-induced tissue damage, mast cells respond to type 1 T cells and produce the two mediators required for the recruitment of PMN into inflamed tissue: the TNF, which induces the expression of intravascular adhesion molecules, and the IL-8, which is the most important chemokine attracting PMN (Biedermann et al. 2000) (Fig. 5B).

Interestingly, mast cells seem not only to recruit PMN during type 1 immune responses. Activated mast cells are also abundant during immunoglob-ulin mediated destruction of the basement membrane in bullous pemphigoid. Adoptive transfer of bullous pemphigoid autoantibodies into the skin of newborn mice underlined that mast cells are required also for PMN recruitment in the pathogenesis of bullous pemphigoid (Chen et al. 2000).

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