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Infection and Immunity, November 2005, p. 7450-7457, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7450-7457.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

In Vitro Effector Activity of Pneumocystis murina-Specific T-Cytotoxic-1 CD8+ T Cells: Role of Granulocyte-Macrophage Colony-Stimulating Factor

Florencia McAllister,1 Chad Steele,1 Mingquan Zheng,1 Judd E. Shellito,2 and Jay K. Kolls1*

Children's Hospital of Pittsburgh, University of Pittsburgh, Department of Pediatrics, Pittsburgh, Pennsylvania 15213,1 LSUHSC Gene Therapy Program, LSUHSC School of Medicine, New Orleans, Louisiana 701122

Received 10 May 2005/ Returned for modification 10 June 2005/ Accepted 25 July 2005

Human immunodeficiency virus (HIV)-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of highly active antiretroviral therapy or nonadherent to HIV care, and other immunosuppressed individuals. One of the most common opportunistic infections in these patients is Pneumocystis pneumonia. CD8+ T cells are recruited to the lung after P. carinii infection and have been associated with both lung injury and host defense. This variability may be due to subpopulations of CD8+ T cells recruited to the lung. We have previously shown using adoptive transfer studies that in vivo-generated T-cytotoxic-1 (Tc1) CD8+ T cells, defined by the secretion of gamma interferon (IFN-{gamma}), have effector activity against Pneumocystis spp. in vitro as well as in vivo. To better understand the mechanisms of these effects, we generated, expanded, and tested Tc1 and Tc2 CD8+ T cells specific for P. murina ex vivo. Tc1-polarized CD8+ T cells secreted higher levels of IFN-{gamma} and granulocyte-macrophage colony-stimulating factor (GM-CSF) and lower levels of interleukin-4 (IL-4), IL-5, IL-10, and IL-13 than Tc2 CD8+ T cells when stimulated with P. murina antigen. Moreover, Tc1 CD8+ T cells demonstrated enhanced effector activity in a macrophage-mediated killing assay which was independent of cell contact. The augmentation in macrophage-mediated P. murina killing was significantly abrogated when GM-CSF was neutralized in the Tc1 CD8+ T cells. These data support the possibility that antigen-specific GM-CSF secretion is critical for effector activity of P. murina-specific Tc1 CD8+ T cells in vitro.

* Corresponding author. Mailing address: Children's Hospital of Pittsburgh, Suite 3765, 3705 Fifth Ave., Pittsburgh, PA 15213. Phone: (412) 692-5630. Fax: (412) 692-6645. E-mail: jay.kolls{at}chp.edu.

Editor: T. R. Kozel

Infection and Immunity, November 2005, p. 7450-7457, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7450-7457.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lasbury, M. E., Durant, P. J., Liao, C.-P., Lee, C.-H. (2009). Effects of Decreased Calmodulin Protein on the Survival Mechanisms of Alveolar Macrophages during Pneumocystis Pneumonia. Infect. Immun. 77: 3344-3354 [Abstract] [Full Text]  
  • Rapaka, R. R., Goetzman, E. S., Zheng, M., Vockley, J., McKinley, L., Kolls, J. K., Steele, C. (2007). Enhanced Defense against Pneumocystis carinii Mediated by a Novel Dectin-1 Receptor Fc Fusion Protein. J. Immunol. 178: 3702-3712 [Abstract] [Full Text]  
  • McAllister, F., Ruan, S., Steele, C., Zheng, M., McKinley, L., Ulrich, L., Marrero, L., Shellito, J. E., Kolls, J. K. (2006). CXCR3 and IFN Protein-10 in Pneumocystis Pneumonia. J. Immunol. 177: 1846-1854 [Abstract] [Full Text]  


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