Killing of antigen-reactive B cells by class II- restricted, soluble antigen–specific CD8+ cytolytic T lymphocytes

Shinohara, Nobukata; Watanabe, Motoó; Sachs, David H.; Hozumi, Nobumichi

doi:10.1038/336481a0

Cited by 82 publications

(30 citation statements)

References 13 publications

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“…The need for T cell help predicts that B lymphocytes are de facto limited in their ability to activate CD8 T cells. Thus, the inappropriate activation of CD8 T cells should remain a rare event and B lymphocytes should be protected from auto-elimination by cytotoxic T lymphocytes [38,39]. Earlier reports showed that B lymphocytes tolerize [6] or anergize [16] CD8 T cells, effects obtained injecting mice with a large number (5Â10 7 ) of autologous B lymphocytes, that is a number equal to the number of B lymphocytes in the spleen.…”

Section: Discussionmentioning

confidence: 99%

CD8 T cell priming by B lymphocytes is CD4 help dependent

Castiglioni¹,

Gerloni²,

Cortez-Gonzalez³

et al. 2005

Eur J Immunol

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While it is generally accepted that B lymphocytes can present antigen and activate CD4 T cells, priming of CD8 T cells by B lymphocytes remains controversial. Recently, we showed that mice injected with genetically programmed B lymphocytes generate antigen specific CD4 and CD8 T cell responses in vivo that could also be induced in mice lacking functional dendritic cells. To gain further insights into the requirements for T cell priming by antigen-presenting B lymphocytes, in vitro experiments were performed using ovalbumin (OVA) and OVA-specific TCR-transgenic CD4 and CD8 T cells. We found that while B lymphocytes can directly prime CD4 T cells, the activation of CD8 T cells requires T cell help. Transfer experiments show that help can either be contact dependent or be mediated by soluble factors in the supernatants of activated OVAspecific CD4 T cells. Furthermore, the effect of activated CD4 T cells can be replaced by soluble recombinant IL-4. Collectively, the data show the existence of different requirements for priming of CD4 and CD8 T cells and point to the previously unappreciated fact that the induction of CD8 T cell responses by B lymphocytes requires T cell help.

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Section: Discussionmentioning

confidence: 99%

CD8 T cell priming by B lymphocytes is CD4 help dependent

Castiglioni¹,

Gerloni²,

Cortez-Gonzalez³

et al. 2005

Eur J Immunol

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“…After informed consent, cells from HLA-A2-positive patients with B-cell malignancies [18 CLL,7 follicular lymphoma, 2 acute lymphocytic leukemia, 1 large cell lymphoma (non-Hodgkin lymphoma)], which were enrolled in clinical trials approved by the institutional review board and healthy individuals (n ϭ 23) were obtained from leucopheresis products. Peripheral blood mononuclear cells were separated using Ficoll-Hypaque gradient-density (Organon Teknika Co., Durham, NC) and were subsequently frozen in RPMI 1640 complete medium (CM; 25 mM HEPES buffer, 2 mM L-glutamine, 100 units/ml penicillin, and 100 g/ml streptomycin; Life Technologies, Inc., Gaithersburg, MD) containing 20% heatinactivated FCS and 10% DMSO according to the standard protocols.…”

Section: Methodsmentioning

confidence: 99%

“…Several recent studies have identified tumor-reactive CD4 ϩ and CD8 ϩ T-lymphocytes in nonHodgkin lymphoma and chronic lymphocytic leukemia (CLL; Refs. [5][6][7][8]. Furthermore, immunoglobulin idiotype vaccination in myeloma and non-Hodgkin lymphoma can induce immune responses to malignant B cells (9 -12).…”

Section: Cd8mentioning

confidence: 99%

Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies

Grube

Rezvani

Wiestner

et al. 2004

Clinical Cancer Research

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Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes.Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-␥ mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients.Results: In healthy individuals, CD8 ؉ T-cell responses were detected in one to CD19 74 -82 , in three to CD20 127-135 , and three to CD20 188 -196 . Seven of 27 patients (6 with CLL) had CD8 ؉ T cells recognizing CD19 74 -82 . Seven patients responded to CD20 127-135 and three to CD20 188 -196 . All were CLL patients. CD19 74 -82 -specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigenpresenting cells but not to malignant or unpulsed B cells.Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.

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“…Repeated nAb escape through high GP sequence variation in the rapidly growing viral quasispecies contributes further to inefficient antibody-mediated virus control (6,7). Additionally, T cell-mediated immunopathologic or suppressive effects on antibody production have been proposed (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Kinetics of protective antibodies are determined by the viral surface antigen

Pinschewer¹,

Perez²,

Jeetendra³

et al. 2004

J. Clin. Invest.

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Delayed and weak virus neutralizing antibody (nAb) responses represent a hallmark correlating not only with the establishment of persistent infection but also with unsuccessful vaccine development. Using a reverse genetic approach, we evaluated possible underlying mechanisms in 2 widely studied viral infection models. Swapping the glycoproteins (GPs) of lymphocytic choriomeningitis virus (LCMV, naturally persisting, noncytolytic, inefficient nAb inducer) and vesicular stomatitis virus (VSV, nonpersisting, cytolytic, potent nAb inducer) transferred the only target of nAb's from either virus to the other. We analyzed the nAb response to each of the 2 recombinant and parent viruses in infected mice and found that nAb kinetics were solely determined by the viral surface GP and not by the virus backbone. Moreover, the slowly and poorly nAb-triggering LCMV virion was a potent immunogenic matrix for the more antigenic VSV-GP. These findings indicate that the viral GP determines nAb kinetics largely independently of the specific viral infection context. They further suggest that structural features of viral GPs or coevolutionary adaptation of the virus's GP to the host's naive B cell repertoire, or both, may critically limit nAb kinetics and improvement of vaccine efficacy.

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Killing of antigen-reactive B cells by class II- restricted, soluble antigen–specific CD8+ cytolytic T lymphocytes

Cited by 82 publications

References 13 publications

CD8 T cell priming by B lymphocytes is CD4 help dependent

CD8 T cell priming by B lymphocytes is CD4 help dependent

Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies

Kinetics of protective antibodies are determined by the viral surface antigen

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