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Characterization of CD3+CD4-CD8- (double negative) T cells in patients with systematic lupus erythematosus (SLE).

Anand, A.; (2003) Characterization of CD3+CD4-CD8- (double negative) T cells in patients with systematic lupus erythematosus (SLE). Doctoral thesis , University of London. Green open access

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease characterized serologically by B cell hyperactivity and a panoply of autoantibodies against nuclear, cytoplasmic and cell surface antigens. It is thought that T cells are involved in this process and more recently it has been suggested that the CD4+ CD8+, i.e.double negative (DN) T cells, might be important. As a start to understanding the contribution of DN T cells to disease pathogenesis in SLE, the percentages of DN T cells were determined and it was found that otp but not y5 DNT cells were significantly increased in patients with SLE when compared to rheumatoid arthritis (RA) (autoimmune controls) and healthy controls. To further establish their participation in the autoimmune reactions in SLE, the activation markers expressed by the DN T cells were examined. It was found that HLA-DR and CD69, and co-stimulatory molecules CD28 and CTLA-4 were all expressed by significantly higher percentages of DNT cells from patients with SLE, than those with RA or healthy controls (HC). More DN T cells from SLE patients were CD45RA+ than from controls, while CD45R0+ were reduced. DN T cells in patients with SLE also showed a more activated phenotype than their CD4+/ CD8+ counterparts. To understand the functional significance in SLE DNT cells, the percentages of SLE otp TCR+ DN T cells containing intracellular IL-4, a Th2 cytokine was determined. Higher percentages of SLE ap TCR DN+ T cells contained DL-4 constitutively than RA or HC. DN T cell populations from patients with SLE showed greater resistance to apoptosis in culture than the conventional CD4/CD8+ cells and DN T cells from healthy controls. High Bcl-2/Bax ratios and higher levels of Bcl-x observed in the DN T cells from patients with SLE could explain their resistance to apoptosis compared to the conventional T cells and DN T cells from healthy controls.

Type: Thesis (Doctoral)
Title: Characterization of CD3+CD4-CD8- (double negative) T cells in patients with systematic lupus erythematosus (SLE).
Identifier: PQ ETD:592581
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by Proquest
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/1445261
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