CD8+ T-cells in psoriatic lesions preferentially use T-cell receptors V beta 3 and/or V beta 13.1 genes.
Restricted T-cell receptor V beta gene use in animal models of autoimmune disease has led to the development of strategies to treat autoimmune disease by targeting the T-cell receptors of the pathogenic T-cells. Restricted T-cell receptor gene use has been noted in human autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. We report here the finding of restricted T-cell receptor gene use in psoriasis vulgaris, as well. Our results show an elevated skin (over PBL) expression of V beta 3 and/or V beta 13.1 messages in the CD8+ T-cells in a majority of patients studied. CDR3 sequence analysis on these two V beta s from the skin demonstrated monoclonality or marked oligoclonality. A second biopsy performed 3.5 to 8 months later in four patients, at the same or different lesions, again revealed an elevated V beta 3 and/or V beta 13.1 expression and clonality. Moreover, in three of the four patients, the same TcR V beta CDR3 rearrangement was found in both biopsies, although there was no V beta CDR3 homology noted between patients. In two patients in which V beta 3 and/or V beta 13.1 was not elevated in the CD8+ T-cell population, an increase in V beta 17 gene use and clonality was found. The persistence of V beta 3- and/or V beta 13.1-bearing CD8+ T-cells in lesions that did not undergo resolution suggests their role as effector cells rather than as regulatory cells. The effector function of these CD8+ T-cells is further supported by the clonality of TcR V beta sequence data, which indicates they are recruited and expanded in situ. The V beta s identified in this study are candidate targets for selective immunotherapeutic intervention in psoriasis.
Chang
J C
JC
Immune Response Corporation, Carlsbad, California 92008, USA.
Smith
L R
LR
Froning
K J
KJ
Schwabe
B J
BJ
Laxer
J A
JA
Caralli
L L
LL
Kurkland
H H
HH
Karasek
M A
MA
Wilkinson
D I
DI
Carlo
D J
DJ
D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D017931:DNA Primers; D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta