HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hargadon, K. M. Articles by Engelhard, V. H. Search for Related Content PubMed PubMed Citation Articles by Hargadon, K. M. Articles by Engelhard, V. H.

Incomplete Differentiation of Antigen-Specific CD8 T Cells in Tumor-Draining Lymph Nodes¹

Kristian M. Hargadon^*, C. Colin Brinkman^*, Stacey L. Sheasley-O’Neill^*, Lisa A. Nichols^*, Timothy N. J. Bullock and Victor H. Engelhard^2,*

^* Department of Microbiology and Carter Immunology Center, University of Virginia Health System, Charlottesville, VA 22908; and Department of Pathology and Human Immune Therapy Center, University of Virginia Health System, Charlottesville, VA 22908

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--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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Public Health Service Grant CA78400 (to V.H.E.) and Howard Temin Award K01 CA095093 (to T.N.J.B.). K.M.H. was supported by Training Grant T32 AI107496. S.L.S.-O. was supported by Training Grant T32 GM007267. L.A.N. was supported by Training Grant T32 GM08136-20.

² Address correspondence and reprint requests to Dr. Victor H. Engelhard, University of Virginia School of Medicine Carter Immunology Center, Box 801386, Charlottesville, VA 22908-1386. E-mail address: vhe{at}virginia.edu

³ Abbreviations used in this paper: LN, lymph node; ₂m, ₂-microglobulin; BM, bone marrow; DC, dendritic cell; BMDC, BM-derived DC; cOVA, cytoplasmic chicken OVA; PT, paratracheal; Tyr₃₆₉, amino acids 369–377 of tyrosinase.

This article has been cited by other articles:

				S. Watanabe, K. Deguchi, R. Zheng, H. Tamai, L.-x. Wang, P. A. Cohen, and S. Shu Tumor-Induced CD11b+Gr-1+ Myeloid Cells Suppress T Cell Sensitization in Tumor-Draining Lymph Nodes J. Immunol., September 1, 2008; 181(5): 3291 - 3300. [Abstract] [Full Text] [PDF]

				L. A. Nichols, Y. Chen, T. A. Colella, C. L. Bennett, B. E. Clausen, and V. H. Engelhard Deletional Self-Tolerance to a Melanocyte/Melanoma Antigen Derived from Tyrosinase Is Mediated by a Radio-Resistant Cell in Peripheral and Mesenteric Lymph Nodes J. Immunol., July 15, 2007; 179(2): 993 - 1003. [Abstract] [Full Text] [PDF]