Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.
To identify disease-specific T cell changes that occur in Crohn's disease (CD), the T cell receptor BV repertoires of lamina propria lymphocytes (LPL) isolated from both the inflamed and "disease-inactive" colons of seven CD patients were compared by the quantitative PCR and DNA sequence analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon from the same individual were very different. Furthermore, nearly all of the differences occurred in CD4+ LPL, with very few differences in the CD8+ population of LPL. Although the pattern of BV segments that was increased in disease-active tissue relative to disease-inactive tissue was different for all seven CD patients, there were several BV segments that increased uniformly in the disease-active tissue of all seven individuals. CDR3 length analysis and DNA sequencing of these BV segments revealed that in six of the seven CD patients there was a striking degree of oligoclonality that was absent from disease-inactive tissue of the same individual. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens. The isolation of such inflammation-specific CD4+ T cells may make it possible to identify the antigens that are responsible for the inflammatory process in CD and provide a better understanding of its pathogenesis.
Gulwani-Akolkar
B
B
Department of Medicine, North Shore University Hospital/Cornell University Medical College, Manhasset, New York 11030, USA.
Akolkar
P N
PN
Minassian
A
A
Pergolizzi
R
R
McKinley
M
M
Mullin
G
G
Fisher
S
S
Silver
J
J
D000293:Adolescent; D000328:Adult; D001485:Basement Membrane / Q000166:cytology / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D002999:Clone Cells / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D017422:Sequence Analysis, DNA
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell