Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis.
A novel subset of T cells characterized by the expression of an invariant T cell antigen receptor (TCR) encoded by V alpha 24J alpha Q gene segments was investigated in patients with systemic sclerosis (SSc). Polymerase chain reaction analysis demonstrated that the V alpha 24 TCR repertoire was selectively used in CD4-CD8- double-negative T cells both in patients and in healthy individuals, while almost all families of TCR V alpha were expressed in single-positive T cell fractions. The V alpha 24+ double-negative T cells were increased by approximately fivefold in patients. However, sequence analysis clearly showed significant differences in the V alpha 24 TCR repertoire dominating in patients and healthy donors. In healthy individuals, the invariant V alpha 24J alpha Q was expanded and comprised 20-50% of the total TCR-alpha, while their selective reduction was observed in SSc patients who also showed expansion of invariant V alpha 24 TCR other than V alpha 24J alpha Q. Analogous to murine invariant V alpha 14J alpha 281 TCR, these results suggest that T cells with invariant V alpha 24J alpha Q TCR would function as regulatory T cells, whereas T cells bearing other invariant V alpha 24 TCR in SSc patients could be autoaggressive T cells in nature.
Sumida
T
T
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Sakamoto
A
A
Murata
H
H
Makino
Y
Y
Takahashi
H
H
Yoshida
S
S
Nishioka
K
K
Iwamoto
I
I
Taniguchi
M
M
D044466:Asian People; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002469:Cell Separation; D003001:Cloning, Molecular; D005434:Flow Cytometry; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000276:immunology*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta