of psoriatic lesional skin T cells compared

with normal, including increased expres-

sion of GATA-3 and STAT-1 transcription

factors and TH1-deviating infl ammatory

cytokines. Furthermore, systemic immune

deviation in psoriasis patients is evidenced

by the threefold increase in circulating

blood TH1 cells compared with normal

controls.

On the basis of fi nding clonal popula-

tions of T cells in psoriatic skin lesions, it

has been hypothesized that pathogenic

T cells are reactive to as yet an unidentifi ed

cutaneous antigen(s) and that the process

of generating skin-homing effector T cells

is initially the same as a normal cellular

response. The formation of psoriatic lesions

differs from lymphocytic infi ltration in

acute hypersensitivity reactions in that

activation does not resolve spontaneously

(as, for example, after the elimination of

an infectious agent). Furthermore, chronic

lesions contain a signifi cant infi ltration of

neutrophils, which is unusual for a “pure”

T-cell-mediated response in the skin.

An alternative hypothesis is that, in the

genetically programmed psoriatic patient,

initial T-cell activation is not necessarily a

reaction to a cutaneous antigen but rather

to bacterial antigens known to be immu-

nologically cross-reactive with keratino-

cytes such as the group A streptococcus.

Evidence for this pathway is suggested by

an elevated immune response to strepto-

coccal antigens in guttate psoriasis and the

presence of antigens similar to streptococ-

cal M proteins in the psoriatic lesions.

The model in Figure 10.1 considers

mainly the pathogenic activity of T cells in

disease pathogenesis, but one must con-

sider the infl uence of the innate immune

response on chronic cellular activation in

psoriasis plaques. Yet, the T-cell model

has been a working hypothesis on which

the therapeutic development of immune-

targeted biological drugs has been based.