Restrictions of T cell receptor beta chain repertoire in the peripheral blood of patients with systemic lupus erythematosus.

Holbrook, Miles; Tighe, Patrick J.; Powell, R J

doi:10.1136/ard.55.9.627

Cited by 32 publications

(35 citation statements)

References 31 publications

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“…Mackus et al reported that, in CLL, the absolute number of CD8 ϩ T cells is often increased, and much of this can be attributed to the increased frequency of CTL specific for persistent viruses, such as CMV (34). In contrast, many studies in other settings suggest that skewed repertoires represent deficits in T cells that correlate with other measures of T cell dysfunction (35,36). Correction of repertoire skewing in other settings such as HIV is associated with improved clinical outcome (16).…”

Section: Discussionmentioning

confidence: 90%

In Vitro Engagement of CD3 and CD28 Corrects T Cell Defects in Chronic Lymphocytic Leukemia

Bonyhadi

Frohlich

Rasmussen

et al. 2005

The Journal of Immunology

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Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of leukemic B cells concomitant with immunological abnormalities and depressed immune responses. The T cell abnormalities found in CLL patients are thought to increase the risk of infection and hamper immune recognition and elimination of leukemic cells. We evaluated whether providing signals through CD3 and CD28 would correct some of these T cell defects. PBMC were incubated with anti-CD3 and anti-CD28 mAbs conjugated to superparamagnetic beads for 12–14 days. This resulted in a 1400-fold increase in T cell numbers. Activated T cells expressed high levels of CD25, CD54, CD137, and CD154, and produced IFN-γ, TNF-α, and GM-CSF. The mean T cell composition of cultures increased from ∼6% to >90% and leukemic B cells decreased from a mean of ∼85% to 0.1% or less. Leukemic B cells up-regulated expression of CD54, CD80, CD86, and CD95. Receptor up-regulation required direct cell contact with the activated T cells and could be blocked with anti-CD154 mAb, suggesting that the CD40-CD40L pathway helped mediate these effects. Poor T cell responses to allostimulation were corrected by the activation and expansion process. The skewing in the TCR repertoire returned to normal, or near normal following the culture process in eight of nine patients with abnormal TCR repertoires. Activated T cells had potent in vitro antileukemic effects in contrast to nonactivated T cells. Based upon these findings, a clinical trial has been initiated to test the potential therapeutic effects of T cells activated using this approach in patients with CLL.

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Section: Discussionmentioning

confidence: 90%

In Vitro Engagement of CD3 and CD28 Corrects T Cell Defects in Chronic Lymphocytic Leukemia

Bonyhadi

Frohlich

Rasmussen

et al. 2005

The Journal of Immunology

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“…For all of these reasons, true clonality in an autoimmune disease is not expected. Indeed, oligoclonality has been reported in studies of experimental autoimmunity in animals [17][18][19] as well as in human rheumatoid arthritis, [22][23][24] systemic lupus erythematosus, 43,44 and IgA nephropathy. 45 Clonal dominance also occurs in viral infection [46][47][48] and in response to tumors and during graft-versus-host disease.…”

Section: Discussionmentioning

confidence: 99%

Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimens

Kook

Risitano

Zhang

et al. 2002

Blood

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We studied the degree and the pattern of skewing of the variable region of ␤-chain (VB) T-cell receptor (TCR) repertoire in aplastic anemia (AA) at initial presentation and after immunosuppression using a high-resolution analysis of the TCR VB complementarity-determining region 3 (CDR3). Age-matched healthy individuals and multitransfused patients with nonimmune-mediated hematologic diseases were used as controls. In newly diagnosed AA, the average frequency of CDR3 size distribution deviation indicative of oligoclonal T-cell proliferation was increased (44% ؎ 33% vs 9% ؎ 9%; P ‫؍‬ .0001); AA patients with human leukocyte antigen (HLA)-DR2 and those with expanded paroxysmal nocturnal hemoglobinuria clones showed more skewed VB repertoires. Nonrandom oligoclonal patterns were found for VB6, VB14-16, VB21, VB23, and VB24 subfamilies in more than 50%, and for VB15, VB21, and VB24 in more than 70% of AA patients with HLA-DR2. Patients received immunosuppression with antithymocyte globulin (ATG)/ cyclosporine (CsA) or cyclophosphamide (CTX) with CsA in combination, and their VB repertoire was reanalyzed after treatment. Whereas no significant change in the degree of VB skewing in patients who had received ATG was seen, patients treated with CTX showed a much higher extent of oligoclonality within all VB families, consistent with a profound and longlasting contraction of the T-cell repertoire. VB analysis did not correlate with the lymphocyte count prior to lymphocytotoxic therapy; however, after therapy the degree of VB skewing was highly reflective of the decrease in lymphocyte numbers, suggesting iatrogenic gaps in the VB repertoire rather than the emergence of clonal dominance. Our data indicate that multiple specific clones mediate the immune process in AA. (Blood. 2002; 99:3668-3675)

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“…15,16 The skewing of CDR3 length in SLE reported by Kalden's group correlated positively with disease activity and these ®ndings have been extended in this issue.…”

Section: T Cells In Systemic Lupus Erythematosusmentioning

confidence: 57%

Peripheral blood CD4/ T cells in systemic lupus erythematosus

Horwitz

2001

Lupus

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Restrictions of T cell receptor beta chain repertoire in the peripheral blood of patients with systemic lupus erythematosus.

Cited by 32 publications

References 31 publications

In Vitro Engagement of CD3 and CD28 Corrects T Cell Defects in Chronic Lymphocytic Leukemia

In Vitro Engagement of CD3 and CD28 Corrects T Cell Defects in Chronic Lymphocytic Leukemia

Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimens

Peripheral blood CD4/ T cells in systemic lupus erythematosus

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