Incomplete differentiation of antigen-specific CD8 T cells in tumor-draining lymph nodes.
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.
Hargadon
Kristian M
KM
Department of Microbiology and Carter Immunology Center, University of Virginia Health System, Charlottesville, VA 22908, USA.
Brinkman
C Colin
CC
Sheasley-O'neill
Stacey L
SL
Nichols
Lisa A
LA
Bullock
Timothy N J
TN
Engelhard
Victor H
VH
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D045142:Cross-Priming; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D009368:Neoplasm Transplantation; D013154:Spleen / Q000276:immunology
D000951:Antigens, Neoplasm