This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lindell, D. M. Articles by Huffnagle, G. B. Search for Related Content PubMed PubMed Citation Articles by Lindell, D. M. Articles by Huffnagle, G. B.

(American Journal of Pathology. 2006;168:847-855.)
© 2006 American Society for Investigative Pathology

Distinct Compartmentalization of CD4⁺ T-Cell Effector Function Versus Proliferative Capacity during Pulmonary Cryptococcosis

Dennis M. Lindell^*, Thomas A. Moore^*, Roderick A. McDonald^*, Galen B. Toews^* and Gary B. Huffnagle^*

From the Department of Internal Medicine,^* the Division of Pulmonary and Critical Care Medicine, the Immunology Graduate Program, and the Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan

The activation and expansion of T cells and their acquisition of effector function are key steps in the development of the adaptive immune response. Most infections are predominantly outside of the lymphoid tissues, and it is unclear at what point developmentally and anatomically T cells acquire effector function in vivo. In these studies, we compared the activation and polarization of T cells during murine pulmonary Cryptococcus neoformans infection in the secondary lymphoid tissues and at the site of primary infection. Few CD4⁺ and CD8⁺ T cells expressed an activated phenotype (CD44^hi, CD25⁺, CD69⁺, CD62L^lo, CD45RB^lo) at the sites of clonal expansion (lymph nodes, spleen, and blood). In contrast, a high percentage of T cells expressed activation markers at the site of primary infection, the lungs. Additionally, the polarization of CD4⁺ T cells to interferon--producing effector cells occurred at the site of infection, the lungs. CD4⁺ and CD8⁺ T cells from secondary lymphoid organs responded to TCR restimulation by proliferating, whereas T cells from the lungs proliferated poorly. This report demonstrates for the first time that T-cell activation and effector function in secondary lymphoid tissues during fungal infection is characteristically different from that at the site of primary infection.

This article has been cited by other articles:

				J. J. Osterholzer, J. L. Curtis, T. Polak, T. Ames, G.-H. Chen, R. McDonald, G. B. Huffnagle, and G. B. Toews CCR2 Mediates Conventional Dendritic Cell Recruitment and the Formation of Bronchovascular Mononuclear Cell Infiltrates in the Lungs of Mice Infected with Cryptococcus neoformans J. Immunol., July 1, 2008; 181(1): 610 - 620. [Abstract] [Full Text] [PDF]

				G.-h. Chen, D. A. McNamara, Y. Hernandez, G. B. Huffnagle, G. B. Toews, and M. A. Olszewski Inheritance of Immune Polarization Patterns Is Linked to Resistance versus Susceptibility to Cryptococcus neoformans in a Mouse Model Infect. Immun., June 1, 2008; 76(6): 2379 - 2391. [Abstract] [Full Text] [PDF]

				D. M. Lindell, M. N. Ballinger, R. A. McDonald, G. B. Toews, and G. B. Huffnagle Immunologic Homeostasis during Infection: Coexistence of Strong Pulmonary Cell-Mediated Immunity to Secondary Cryptococcus neoformans Infection While the Primary Infection Still Persists at Low Levels in the Lungs J. Immunol., October 1, 2006; 177(7): 4652 - 4661. [Abstract] [Full Text] [PDF]