CD4+ cell oligoclonality in Crohn's disease: evidence for an antigen-specific response.
To identify disease-specific T cell changes that occur in Crohn's disease (CD) the T-cell receptor (TCR) BV repertoires of lamina propria lymphocytes (LPL) from both disease-active and disease-inactive colonic tissue of three CD patients were compared by a quantitative polymerase chain reaction (qPCR) and CDR3 length analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon of the same individual were different, and most of the differences occurred in CD4+ LPL with very few differences in the CD8+ populations of LPL. Although the pattern of BV segments that was increased in disease-active relative to disease-inactive tissue was different for all three CD patients, there was an increase in the levels of BV11, 13S2, 15, 16, and 17 segments in the disease-active tissue of all three patients. Standard CDR3 length analysis of BV11, 13S2, 15, 16, and 17 segments revealed that in two of the three CD patients there was a striking degree of TCR oligoclonality in the disease-active tissue that was absent from disease-inactive tissue of the same individual. Additional differences between the disease-active and disease-inactive tissues were observed using a more refined method of CDR3 length analysis, which employs BV- and BJ-specific primers. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens.
Gulwani-Akolkar
B
B
Division of Molecular Medicine, Department of Medicine, North Shore University Hospital/Cornell University Medical College, Manhasset, New York, USA.
Akolkar
P N
PN
Minassian
A
A
McKinley
M
M
Fisher
S
S
Silver
J
J
D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000276:immunology*; D001483:Base Sequence / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003001:Cloning, Molecular; D003424:Crohn Disease / Q000276:immunology*; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis
D000941:Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta