CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

ABSTRACT A previous study of the murine model of Schistosoma mansoni infection has implicated splenic CD19+ B lymphocytes as Fas ligand (FasL)-bearing mediators of CD4+ T-lymphocyte apoptosis. The present study shows that B-cell deficiency leads to decreased CD4+ T-cell apoptosis during infection and compares FasL expression and killer function of B-1a- and CD5− B-lymphocyte subsets. B-1a cells from uninfected mice displayed constitutive expression of FasL compared with that of CD5− B cells. FasL expression was enhanced following worm egg deposition and antigenic stimulation on both subsets of B cells. Purified B-1a cells from uninfected mice were potent effectors of CD4+ T-cell apoptosis, and the killing effect was enhanced during schistosome infection. FasL expression by splenic B cells required CD4+-T-cell help that was replaced by addition of culture supernatants from antigen-stimulated splenocytes of infected mice. The culture-supernatant-stimulated FasL expression was inhibited by anti-interleukin 10 (IL-10) and anti-IL-4 antibodies. Culture of purified B cells with recombinant IL-4 (rIL-4), rIL-10, and soluble egg antigens (SEA) led to increased expression of FasL on B-1a cells. These results suggest that FasL-expressing, splenic B-1a cells are important mediators of SEA-stimulated CD4+-T-cell apoptosis and that maximal FasL expression on B-1a cells is dependent on antigenic stimulation and the presence of IL-4 and IL-10.

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Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL+ T and B Cells during Murine Schistosoma mansoni Infection

Infection and Immunity ◽

10.1128/iai.69.1.271-280.2001 ◽

2001 ◽

Vol 69 (1) ◽

pp. 271-280 ◽

Cited By ~ 68

Author(s):

Steven K. Lundy ◽

Stephen P. Lerman ◽

Dov L. Boros

Keyword(s):

T Cells ◽

Cell Death ◽

T Cell ◽

B Cells ◽

Cell Apoptosis ◽

Granuloma Formation ◽

Fasl Expression ◽

T Cell Apoptosis ◽

Th Cell ◽

Th Lymphocytes

ABSTRACT Granuloma formation around schistosomal eggs is induced by soluble egg antigens (SEA) and mediated by the activity of CD4+ Th lymphocytes and their cytokines. Regulation of the inflammatory Th cell response during infection is still insufficiently understood. The hypothesis of this study was that activation-induced cell death (AICD) of CD4+ T cells is involved in the immune inflammatory response. This study investigated the dynamics of splenic and granuloma CD4+ Th cell apoptosis and Fas ligand (FasL) expression during the acute and chronic stages of murine schistosomal infection. Enhanced apoptosis of freshly isolated CD4+ Th lymphocytes commenced after egg deposition and persisted during the peak and modulated phases of granuloma formation. After oviposition, CD4+, CD8+, and CD19+ splenocytes and granuloma cells expressed elevated levels of FasL but FasL expression declined during the downmodulated stage of infection. In culture, SEA induced splenic and granuloma CD4+ T-cell apoptosis and stimulated expression of FasL on splenic but not granuloma CD4+ T cells, CD8+ T cells, and CD19+ B cells. SEA-stimulated splenocytes and granuloma cells preferentially lysed a Fas-transfected target cell line. Depletion of B cells from SEA-stimulated splenic cultures decreased CD4+ T cell apoptosis. Coculture of purified splenic B cells with CD4+ T cells and adoptive transfer of purified B cells indicated that antigen-stimulated B cells can kill CD4+ Th cells. However, CD4+ T cells were the dominant mediators of apoptosis in the granuloma. This study indicates that AICD is involved in the apoptosis of CD4+ T cells during schistosomal infection.

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Epstein-Barr Virus Induces Fas (CD95) in T Cells and Fas Ligand in B Cells Leading to T-Cell Apoptosis

Blood ◽

10.1182/blood.v94.10.3439.422k23_3439_3447 ◽

1999 ◽

Vol 94 (10) ◽

pp. 3439-3447 ◽

Cited By ~ 42

Author(s):

Jerome E. Tanner ◽

Caroline Alfieri

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Cell Apoptosis ◽

Cd4 T Cells ◽

Epstein Barr Virus ◽

Fas Ligand ◽

Barr Virus ◽

T Cell Apoptosis ◽

Epstein Barr

Epstein-Barr virus (EBV) acute infectious mononucleosis (AIM) is characterized by transient immunosuppression in vivo and increased T-cell apoptosis after ex vivo culture of AIM peripheral blood mononuclear cells. We undertook experiments to test whether EBV or purified virion envelope glycoprotein gp350 could contribute to Fas-mediated T-cell apoptosis. Our in vitro results indicate that EBV increased Fas expression in CD4+ T cells and Fas ligand (FasL) expression in B cells and macrophages. Purified gp350 was also shown to significantly increase CD95 expression in CD4+ T cells. When T-cell CD95 was cross-linked, EBV-stimulated T cells underwent apoptosis. The induction of T-cell CD95 by EBV followed by CD95 cross-linking with anti-CD95 monoclonal antibody resulted in a loss in the number of T cells responding to the T-cell mitogens, anti-CD3 antibody, and interleukin-2. These results indicate that, in addition to serving as a principal ligand for the attachment of virus to target cells, gp350 may also act as an immunomodulatory molecule that promotes T-cell apoptosis.

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