Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Altered T Cell Signaling in Systemic Lupus Erythematosus (SLE): A Role for FcRIII and Immune Complexes (ICs).

Chauhan1,  Anil, Atkinson3,  John P., Moore2,  Terry L.

Saint Louis University, Saint Louis, MO
St Louis University, St Louis, MO
Washington University School of Medicine, St Louis, MO

Purpose:

The presence of immune complexes (ICs) in systemic lupus erythematosus (SLE) has been documented. In addition, a role for altered T cell responses has been suggested. Previously, we have shown the activation of T cell receptor (TCR) in response ICs and sublytic dose of memebrnae attack complex (MAC). In this study, we wanted to explore the presence of low affinity FcgRIII that are responsible for ICs binding to human peripheral naive CD4+ T cells and explore their downstream signaling partners.

Methods:

We used Alexa Floour 488 labeled model ICs to develop a flow based assay to evaluate the presence of the Fc receptor (FcR) on CD4+ human naïve T cells. Thereafter, we used antibodies specific to FcgRIIIA/B or FcgRIIIB to achieve a 50% inhibition of the labeled IC binding. Subsequently, using immunoprecipitates generated from T cells treated with ICs purified from SLE patients plasama and Western blotting we explored the presence of FcgRIII. Furthermore, we co-localized the FcgRIIIA/B, FcRg-chain and phosphorylated Syk in human naïve CD4+T cells using confocal microscopy. In the immunoprecipitates generated with anti-FcgRIII, we analyzed the phosphorylation of Syk in response to ICs. The phopshorylated Syk was co-localizated with FcgRIII with confocal microscopy. The presence of the IC binding FcgRIII was carried out from peripheral CD4+ T cells from SLE patients by flow cytometry.

Results:

Human peripheral naive CD4+ T cells show binding to labeled ICs. We show a 27 to 29 kD protein that correspond to previously reported mass for FcgRIIIA/B in the CD4+ T cells. A total of 5 to 10% peripheral CD4+ T cells from SLE patients show binding to labeled model ICs. The antibodies against FcgRIIIB and FcgRIIIA/B inhibited binding of labeled ICs by 50%. Upon treatment with ICs, the cells show recruitment of FcRg chain with FcgRIIIA/B. Treatment of cells with ICs and sublytic MAC resulted in phosphorylation and association of Syk with FcgRIIIA.

Conclusions:

For the first time, we show the presence of low affinity FcgRIIIA/B on human CD4+T cells. FcR play critical role in B cell responses and are critical in IC clearance. However, the presence of FcR on human T cell is controversial (Nature reviews,(8) 34,2008). Although, the presence of FcgRIIIA has been shown in NKT and gd T cells, the FcgRIIIB is only known to be expressed by neutrophils and macrophages and is shown on basophils recently. Using an antibody specific for FcgRIIIB, we demonstrate inhibition of model IC binding in flow based assay. We further show upon treatment of these cells with ICs, the FcRg is recruited to the FcgRIIIA receptor. This also resulted in phosphorylation and recruitment of Syk with FcgR. Altered Syk mediated T cell signaling in SLE T cells has been reported earlier. We show that ICs and sublytic MAC activates Syk in peripheral T cells. The naïve CD4+ T cells also proliferate in response to IC and sublytic MAC. We have previously shown TCR activation and T cell differentiation in response to ICs and sublytic MAC. It is for the first time, we demonstrate a possible role for FcR in activation of T cells in response to ICs and MAC, a complex of late complement cascade. This study provides a link between ICs, complement, and adaptive immunity.

To cite this abstract, please use the following information:
Chauhan, Anil, Atkinson, John P., Moore, Terry L.; Altered T Cell Signaling in Systemic Lupus Erythematosus (SLE): A Role for FcRIII and Immune Complexes (ICs). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :846
DOI: 10.1002/art.28614

Abstract Supplement

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