Evaluation of the percentage of peripheral T cells with two different T cell receptor alpha-chains and of their potential role in autoimmunity

Corthay, AlexandreUniversity of Oslo, National Hospital, Oslo, Norway; Lund University, Lund, Sweden (författare)

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. © 2001 Academic Press.

Nandakumar, Kutty Selva,1965-Lund University, Lund, Sweden(Swepub:hh)kutnam (författare)
Holmdahl, RikardLund University, Lund, Sweden (författare)
University of Oslo, National Hospital, Oslo, Norway; Lund University, Lund, SwedenLund University, Lund, Sweden (creator_code:org_t)

Ingår i:Journal of AutoimmunityRockville, MD : American Association of Immunologists16:4, s. 423-4290896-84111095-9157

Av författaren/redakt...: Corthay, Alexand ...; Nandakumar, Kutt ...; Holmdahl, Rikard

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