Evaluation of the percentage of peripheral T cells with two different T cell receptor alpha-chains and of their potential role in autoimmunity.
Approximately 25% of mature T cells possess two distinct cytoplasmic T cell receptor (TCR) alpha-chains, due to productive gene rearrangements of both alleles. Expression of two different alpha-chains at the cell surface is a potential risk factor for development of autoimmunity. However, it has been difficult to determine the frequency of peripheral T cells with two different alpha-chains at the surface. Our new approach is based on comparing by flow cytometry the percentage of cells that express a given Valpha-chain between wild-type mice and mice that are hemizygous for a disrupted Tcra locus (Tcra+/-) and consequently unable to express two rearranged Tcra genes. We consistently found that approximately 8% of total peripheral T cells express two surface alpha-chains. The importance of dual alpha-T cells in autoimmunity was examined in a mouse model for rheumatoid arthritis, namely collagen-induced arthritis (CIA). No significant difference was observed between Tcra+/- mice and wild-type littermates, considering arthritis incidence, day of disease onset, and maximum arthritic score. We therefore conclude that there is incomplete phenotypic allelic exclusion in TCRalpha, and that the presence of a significant number of potentially multireactive T cells does not increase the susceptibility to develop autoimmune arthritis.
Corthay
A
A
Institute of Immunology, University of Oslo, The National Hospital, Oslo, 0027, Norway. Alexandre.Corthay@labmed.uio.no
Nandakumar
K S
KS
Holmdahl
R
R
D000818:Animals; D001168:Arthritis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta