Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells

Albert, Matthew L.; Jegathesan, M; Darnell, Robert B.

doi:10.1038/ni722

Cited by 361 publications

(290 citation statements)

References 37 publications

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“…but the cells apoptose and/or fail to accumulate (50,51). Proliferation leading to accumulation in the absence of effector function has been described for CD8 T cells activated by artificial APC (52).…”

Section: Discussionmentioning

confidence: 99%

Incomplete Differentiation of Antigen-Specific CD8 T Cells in Tumor-Draining Lymph Nodes

Hargadon

Brinkman

Sheasley-O’Neill

et al. 2006

The Journal of Immunology

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CD8 T cells lacking effector activity have been recovered from lymphoid organs of mice and patients with progressing tumors. We explored the basis for lack of effector activity in tumor-bearing mice by evaluating Ag presentation and CD8 T cell function in lymphoid organs over the course of tumor outgrowth. Early after tumor injection, cross-presentation by bone marrow-derived APC was necessary for T cell activation, inducing proliferation and differentiation into IFN-γ-producing, cytolytic effectors. At later stages of outgrowth, tumor metastasized to draining lymph nodes. Both cross- and direct presentation occurred, but T cell differentiation induced by either modality was incomplete (proliferation without cytokine production). T cells within tumor-infiltrated nodes differentiated appropriately if Ag was presented by activated, exogenous dendritic cells. Thus, activated T cells lacking effector function develop through incomplete differentiation in the lymph nodes of late-stage tumor-bearing mice, rather than through suppression of previously differentiated cells.

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Section: Discussionmentioning

confidence: 99%

Incomplete Differentiation of Antigen-Specific CD8 T Cells in Tumor-Draining Lymph Nodes

Hargadon

Brinkman

Sheasley-O’Neill

et al. 2006

The Journal of Immunology

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“…These immature DCs express lower levels of major histocompatibility complex molecules and lack the expression of co-stimulatory molecules at the time of antigen presentation. There is evidence, however, that mature APCs can also induce tolerance (Albert et al, 2001;Menges et al, 2002). We have shown that IDOexpressing APCs, both immature and mature, inhibit antigen-driven proliferation of lymphocytes in mixedleukocyte reactions .…”

Section: Lee Et Almentioning

confidence: 99%

“…There is increasing evidence that antigen presentation by certain bone marrow-derived antigenpresenting cells (APCs) is an important initiator of immunologic self-tolerance (Albert et al, 2001;Dhodapkar et al, 2001;Doan et al, 2000;Jonuleit et al, 2001;Pardoll, 2001;Sotomayor et al, 2001;Steinman and Nussenzwieg, 2002). The characterization of these cells and the mechanism of in vivo tolerance induction, however, is still elusive.…”

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confidence: 99%

Pattern of Recruitment of Immunoregulatory Antigen-Presenting Cells in Malignant Melanoma

Lee

Dalton

Messina

et al. 2003

Laboratory Investigation

104

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SUMMARY:The mechanism by which the immune system of a tumor-bearing host acquires tolerance toward tumor antigens is still elusive. Antigen-presenting cells (APCs) are critical regulators of the decision between immune response and tolerance. APCs that express the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) have been found to inhibit T-cell responses both in vitro and in vivo. We hypothesized that malignant tumors exploit this mechanism by recruiting IDO-expressing APCs to the tumor-draining lymph nodes. To test this hypothesis, archival tissues and records of 26 cases of lymph node dissection for invasive cutaneous melanoma were obtained. IDO immunohistochemistry was performed on 14 cutaneous tumors and 328 regional lymph nodes. Abnormal accumulations of IDO-positive cells with a monocytoid or plasmacytoid morphology were identified in the perisinusoidal regions of draining lymph nodes in 45% of nodes studied. Recruitment of IDO-positive cells was seen in nodes with and without malignancy. We hypothesize that these IDO-positive APCs may contribute mechanistically to acquired tolerance to tumor antigens. Immunostaining of tumor-draining lymph nodes for abnormal accumulation of IDOexpressing cells might thus constitute an adverse prognostic factor and could contribute to the decision process and the appropriate care of patients with this deadly disease. (Lab Invest 2003, 83:1457-1466.

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“…In particular, CD4 ϩ T cells have been shown to play a critical role in tumor eradication when CD8 ϩ T cell numbers are suboptimal (21), to be involved in both CD8 ϩ T cell maintenance and tumor mass infiltration (22), to be important for the recruitment of antitumor effector cells to the tumor mass (23), as well as to have direct antitumor effector functions (24). CD4 ϩ T cells have also been shown to be important for the maturation of DC, a process critical for the effective activation of the Ag-specific CD8 ϩ T cell compartment (25). Finally, the activation of tumor Ag-specific CD4 ϩ T cell help is an important prerequisite for the subsequent development of a humoral antitumor response.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen

Friedman

Bangur

Zasloff

et al. 2004

The Journal of Immunology

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The developmental transcription factor SOX-4 has been shown to be highly and differentially overexpressed in primary small cell lung carcinomas (SCLC). To examine the potential of SOX-4 for broad use as a lung cancer vaccine, we have evaluated the expression of SOX-4 in a panel of primary adenocarcinoma, squamous, and large cell tumor samples as well as in a panel of established small cell and non-small cell lung carcinoma tumor cell lines. SOX-4 mRNA is shown to be overexpressed in a substantial fraction of each of these lung tumor types. To examine the immunological potential of SOX-4, we have evaluated the presence of SOX-4-specific CD4 and CD8 T cells in PBMC of healthy donors and the presence of SOX4-specific Abs in sera from SCLC patients. We demonstrate the presence of both CD4 and CD8 T cells that recognize naturally processed epitopes derived from SOX-4 as well as the presence of SOX-4-specific Abs in sera from SCLC patients, but not in sera from healthy donors. The lung tumor-specific overexpression and demonstration of a comprehensive Ag-specific immune response specific for SOX-4 support the use of this molecule in the development of whole gene-, peptide-, or protein-based vaccination strategies against lung cancer. Furthermore, the identification of naturally processed T cell and Ab epitopes from SOX-4 provides valuable tools for the development of peptide-based vaccination strategies against lung cancer as well as to monitor SOX-4-specific responses in vaccinated patients.

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Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells

Cited by 361 publications

References 37 publications

Incomplete Differentiation of Antigen-Specific CD8 T Cells in Tumor-Draining Lymph Nodes

Incomplete Differentiation of Antigen-Specific CD8 T Cells in Tumor-Draining Lymph Nodes

Pattern of Recruitment of Immunoregulatory Antigen-Presenting Cells in Malignant Melanoma

Molecular and Immunological Evaluation of the Transcription Factor SOX-4 as a Lung Tumor Vaccine Antigen

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