期刊
JOURNAL OF IMMUNOLOGY
卷 177, 期 9, 页码 6081-6090出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.177.9.6081
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资金
- NCI NIH HHS [CA 78400, K01 CA 095093] Funding Source: Medline
- NIAID NIH HHS [T32 AI055432, T32 AI007046, T32 AI 107496] Funding Source: Medline
- NIGMS NIH HHS [T32 GM 007267, T32 GM 08136-20] Funding Source: Medline
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-gamma-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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