Excessive costimulation of CD3-dependent lymphocyte response by extracellular matrix proteins in severe widespread psoriasis

Abstract

Costimulation of anti-CD3-triggered proliferative T-cell responses by type I and type IV collagen and fibronectin was studied in 25 patients with psoriasis and 12 healthy subjects. The stimulation index of anti-CD3-mediated responses in the presence of type I collagen was about half that in the controls. Although the CD3-dependent proliferative response of psoriatic lymphocytes in patients with active widespread plaque psoriasis was reduced by about 50%, costimulatory responses induced by type IV collagen and fibronectin were found to be enhanced in relation to the controls. The degree of costimulation by type IV collagen and fibronectin was related to disease severity. The highest values of the stimulation index were found in patients with a PASI greater than 24, skin involvement of more than 40% of body surface area, and a duration of psoriatic lesions of more than 3 months. The results indicated that in active widespread plaque psoriasis subpopulations of T cells bearing receptors for some extracellular matrix proteins were increased in the peripheral blood. A factor responsible for this phenomenon may be trafficking of T cells through the basement membrane zone of psoriatic lesions, which presumably causes modification of T cell immunological responsiveness after recirculation.

T Cell Epitope-Specific Defects in the Immune Response to Cat Allergen in Patients with Atopic Dermatitis

“…Furthermore, T cell proliferation and IFN-g responses in unstimulated cultures were high in the absence of anti-IL-10 mAb suggesting endogenous T cell or monocyte activation. Indeed, spontaneous proliferation and cytokine production by cells derived from AD patients have been reported (Glinski et al, 1995;Poulsen et al, 1995;Akdis et al, 1999). Thus, it could be argued that the effects of blocking IL-10 in these patients are non-specific.…”

Profiles of Activated T Lymphocytes in Peripheral Blood of Kuwaiti Psoriasis Vulgaris Patients

“…To address this issue more definitively, we profiled the lymphocyte subpopulations in Kuwaiti psoriatics. Psoriasis is characterized by increased subpopulations of peripheral blood T cells bearing receptors for extracellular matrix proteins; activation of these cells correlates positively with progression of the disease (19). These characteristics are expected to mediate decreases in overall numbers of T and B lymphocytes due to induction of activation‐induced cell death (AICD) (20).…”

Interaction Between Fibronectin and Eosinophils in the Growth of Nasal Polyps

“…On the other hand, infiltration of eosinophils and the expression of fibronectin showed significant correlation. Fibronectin is closely related to activation and infiltration of inflammatory cells 13‐20 . Among inflammatory cells, interaction of eosinophils and fibronectin has been well documented.…”

“…There are some indications that cytokines associated with eosinophils and accumulation of the extracellular matrix are involved in the growth of nasal polyps 3‐10 . Fibronectin, one of the extracellular matrix proteins, is known to be related in some way to inflammatory responses 11‐20 . Therefore, an integrated process of eosinophils, cytokines, and fibronectin was predicted to play a key role in the pathogenesis of nasal polyposis.…”