The role of immune system in the pathogenesis of psoriasis.
Psoriatic involved skin contains an increased number of activated T cells. The mechanism through which these T cells achieve and maintain their activated state is unknown, and both antigen-dependent and -independent mechanisms may contribute. Recently a novel pathway of antigen-independent T-cell activation has been described. This pathway is identified by a monoclonal antibody that binds to a T-cell membrane surface molecule termed "UM4D4." This molecule is expressed on a minority (20%) of psoriatic peripheral blood T cells but on a majority (75%) of the T cells in lesional skin. Thus, UM4D4 could play a role in antigen-independent T-cell activation in psoriasis. Indeed the monoclonal antibody anti-UM4D4 consistently induces proliferation of psoriatic UM4D4+ T-cell clones. The activity of antigen-dependent pathways are also enhanced in psoriatic epidermis in as much as involved skin relative to uninvolved skin contains an increased number and function of antigen-presenting cells. Upon activation, the lesional T cells release lymphokines. Central to the immune hypothesis of psoriasis is that some of these T-cell lymphokines act on keratinocytes to induce changes characteristic of psoriasis. Indeed lymphokines from lesional psoriatic T-cell clones directly alter in vitro keratinocyte phenotype through induction of intercellular adhesion molecule-I (ICAM-1) and HLA-DR cell-surface expression. Furthermore, the lymphokines also enhance keratinocyte growth. These data suggest a critical role for the immune system in the pathogenesis of psoriasis.
Baadsgaard
O
O
Department of Dermatology, University of Michigan Medical School, Ann Arbor, USA.
Fisher
G
G
Voorhees
J J
JJ
Cooper
K D
KD
D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007107:Immune System / Q000502:physiology*; D015603:Keratinocytes / Q000502:physiology; D008213:Lymphocyte Activation; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C064741:CDw60 antigen; D006684:HLA-DR Antigens