Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells

doi:10.1084/jem.173.4.793

This Article

	Full Text (PDF, 875K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Huffnagle, G. B.
	Articles by Lipscomb, M. F.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Huffnagle, G. B.
	Articles by Lipscomb, M. F.


Social Bookmarking

	What's this?

ARTICLES

Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells

GB Huffnagle, JL Yates and MF Lipscomb
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235.

The role of CD4+ and CD8+ T cells in mediating pulmonary clearance of a cryptococcal infection was investigated. Intratracheal inoculation of BALB/c and C.B-17 mice with a moderately virulent strain of Cryptococcus neoformans (52D) resulted in a pulmonary infection, which was cleared by a T cell-dependent mechanism. During this clearance, there was a significant influx of both CD4+ and CD8+ T cells into the lungs. Depletion of CD4+ T cells by injections of CD4-specific monoclonal antibody (mAb) prevented pulmonary clearance and also resulted in significant colonization of the brain and spleen of infected mice. CD4 depletion did not prevent the influx of CD8+ T cells into the lungs. Surprisingly, depletion of CD8+ T cells by mAb also ablated pulmonary clearance. CD8-depleted mice also had a small but significant increase in brain and spleen colony-forming unit compared to control mice by the end of the study. CD4+ T cell pulmonary influx was independent of the presence of CD8+ T cells. The lungs of T cell- depleted mice were examined histologically. CD4+ and CD8+ T cells each mediated a degree of inflammatory influx seen in the lungs of infected mice and raised the possibility that CD4+ and CD8+ T cells may synergize to generate the inflammatory response in the lungs. Numerous phagocytized but intact cryptococci were seen in the inflammatory foci of CD8-depleted mice but not in control or CD4-depleted mice. We propose that CD4+ T cells may recruit and activate effector phagocytes while CD8+ T cells predominantly function to lyse cryptococcus-laden unactivated phagocytes similar to the function of CD8+ T cells during listeria and mycobacteria infections.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Wozniak, K. L., Levitz, S. M. (2008). Cryptococcus neoformans Enters the Endolysosomal Pathway of Dendritic Cells and Is Killed by Lysosomal Components. Infect. Immun. 76: 4764-4771 [Abstract] [Full Text]
Guillot, L., Carroll, S. F., Homer, R., Qureshi, S. T. (2008). Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection. Infect. Immun. 76: 4745-4756 [Abstract] [Full Text]
Osterholzer, J. J., Curtis, J. L., Polak, T., Ames, T., Chen, G.-H., McDonald, R., Huffnagle, G. B., Toews, G. B. (2008). 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. 181: 610-620 [Abstract] [Full Text]
Chen, G.-h., McNamara, D. A., Hernandez, Y., Huffnagle, G. B., Toews, G. B., Olszewski, M. A. (2008). Inheritance of Immune Polarization Patterns Is Linked to Resistance versus Susceptibility to Cryptococcus neoformans in a Mouse Model. Infect. Immun. 76: 2379-2391 [Abstract] [Full Text]
Zaragoza, O., Alvarez, M., Telzak, A., Rivera, J., Casadevall, A. (2007). The Relative Susceptibility of Mouse Strains to Pulmonary Cryptococcus neoformans Infection Is Associated with Pleiotropic Differences in the Immune Response. Infect. Immun. 75: 2729-2739 [Abstract] [Full Text]
Chen, G.-H., Olszewski, M. A., McDonald, R. A., Wells, J. C., Paine, R. III, Huffnagle, G. B., Toews, G. B. (2007). Role of Granulocyte Macrophage Colony-Stimulating Factor in Host Defense Against Pulmonary Cryptococcus neoformans Infection during Murine Allergic Bronchopulmonary Mycosis. Am. J. Pathol. 170: 1028-1040 [Abstract] [Full Text]
Lindell, D. M., Ballinger, M. N., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2006). 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. 177: 4652-4661 [Abstract] [Full Text]
Tao, J., Segal, B. H., Eppolito, C., Li, Q., Dennis, C. G., Youn, R., Shrikant, P. A. (2006). Aspergillus fumigatus extract differentially regulates antigen-specific CD4+ and CD8+ T cell responses to promote host immunity. J. Leukoc. Biol. 80: 529-537 [Abstract] [Full Text]
Lindell, D. M., Ballinger, M. N., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2006). Diversity of the T-Cell Response to Pulmonary Cryptococcus neoformans Infection.. Infect. Immun. 74: 4538-4548 [Abstract] [Full Text]
Wozniak, K. L., Vyas, J. M., Levitz, S. M. (2006). In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis. Infect. Immun. 74: 3817-3824 [Abstract] [Full Text]
Arora, S., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2006). Effect of a CD4-Depleting Antibody on the Development of Cryptococcus neoformans-Induced Allergic Bronchopulmonary Mycosis in Mice. Infect. Immun. 74: 4339-4348 [Abstract] [Full Text]
Zhou, Q., Gault, R. A., Kozel, T. R., Murphy, W. J. (2006). Immunomodulation with CD40 Stimulation and Interleukin-2 Protects Mice from Disseminated Cryptococcosis. Infect. Immun. 74: 2161-2168 [Abstract] [Full Text]
Lindell, D. M., Moore, T. A., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2006). Distinct Compartmentalization of CD4+ T-Cell Effector Function Versus Proliferative Capacity during Pulmonary Cryptococcosis. Am. J. Pathol. 168: 847-855 [Abstract] [Full Text]
Lindell, D. M., Moore, T. A., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2005). Generation of Antifungal Effector CD8+ T Cells in the Absence of CD4+ T Cells during Cryptococcus neoformans Infection. J. Immunol. 174: 7920-7928 [Abstract] [Full Text]
Chen, G.-H., McDonald, R. A., Wells, J. C., Huffnagle, G. B., Lukacs, N. W., Toews, G. B. (2005). The Gamma Interferon Receptor Is Required for the Protective Pulmonary Inflammatory Response to Cryptococcus neoformans. Infect. Immun. 73: 1788-1796 [Abstract] [Full Text]
Rivera, J., Zaragoza, O., Casadevall, A. (2005). Antibody-Mediated Protection against Cryptococcus neoformans Pulmonary Infection Is Dependent on B Cells. Infect. Immun. 73: 1141-1150 [Abstract] [Full Text]
Uezu, K., Kawakami, K., Miyagi, K., Kinjo, Y., Kinjo, T., Ishikawa, H., Saito, A. (2004). Accumulation of {gamma}{delta} T Cells in the Lungs and Their Regulatory Roles in Th1 Response and Host Defense against Pulmonary Infection with Cryptococcus neoformans. J. Immunol. 172: 7629-7634 [Abstract] [Full Text]
Humphreys, I. R., Edwards, L., Walzl, G., Rae, A. J., Dougan, G., Hill, S., Hussell, T. (2003). OX40 Ligation on Activated T Cells Enhances the Control of Cryptococcus neoformans and Reduces Pulmonary Eosinophilia. J. Immunol. 170: 6125-6132 [Abstract] [Full Text]
Wuthrich, M., Filutowicz, H. I., Warner, T., Deepe, G. S. Jr., Klein, B. S. (2003). Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells: Implications for Vaccine Development in Immune-deficient Hosts. JEM 197: 1405-1416 [Abstract] [Full Text]
Taborda, C. P., Rivera, J., Zaragoza, O., Casadevall, A. (2003). More Is Not Necessarily Better: Prozone-Like Effects in Passive Immunization with IgG. J. Immunol. 170: 3621-3630 [Abstract] [Full Text]
Ma, L. L., Spurrell, J. C. L., Wang, J. F., Neely, G. G., Epelman, S., Krensky, A. M., Mody, C. H. (2002). CD8 T Cell-Mediated Killing of Cryptococcus neoformans Requires Granulysin and Is Dependent on CD4 T Cells and IL-15. J. Immunol. 169: 5787-5795 [Abstract] [Full Text]
Syme, R. M., Spurrell, J. C. L., Amankwah, E. K., Green, F. H. Y., Mody, C. H. (2002). Primary Dendritic Cells Phagocytose Cryptococcus neoformans via Mannose Receptors and Fc{gamma} Receptor II for Presentation to T Lymphocytes. Infect. Immun. 70: 5972-5981 [Abstract] [Full Text]
Herring, A. C., Lee, J., McDonald, R. A., Toews, G. B., Huffnagle, G. B. (2002). Induction of Interleukin-12 and Gamma Interferon Requires Tumor Necrosis Factor Alpha for Protective T1-Cell-Mediated Immunity to Pulmonary Cryptococcus neoformans Infection. Infect. Immun. 70: 2959-2964 [Abstract] [Full Text]
Mansour, M. K., Schlesinger, L. S., Levitz, S. M. (2002). Optimal T Cell Responses to Cryptococcus neoformans Mannoprotein Are Dependent on Recognition of Conjugated Carbohydrates by Mannose Receptors. J. Immunol. 168: 2872-2879 [Abstract] [Full Text]
Wilder, J. A., Olson, G. K., Chang, Y. C., Kwon-Chung, K. J., Lipscomb, M. F. (2002). Complementation of a Capsule Deficient Cryptococcus neoformans with Cap64 Restores Virulence in a Murine Lung Infection. Am. J. Respir. Cell Mol. Bio. 26: 306-314 [Abstract] [Full Text]
Kawakami, K., Kinjo, Y., Uezu, K., Yara, S., Miyagi, K., Koguchi, Y., Nakayama, T., Taniguchi, M., Saito, A. (2001). Monocyte Chemoattractant Protein-1-Dependent Increase of V{alpha}14 NKT Cells in Lungs and Their Roles in Th1 Response and Host Defense in Cryptococcal Infection. J. Immunol. 167: 6525-6532 [Abstract] [Full Text]
Almeida, G. M., Andrade, R. M., Bento, C. A. M. (2001). The Capsular Polysaccharides of Cryptococcus neoformans Activate Normal CD4+ T Cells in a Dominant Th2 Pattern. J. Immunol. 167: 5845-5851 [Abstract] [Full Text]
Moore, B.B., Moore, T.A., Toews, G.B. (2001). Role of T- and B-;lymphocytes in pulmonary host defences. Eur Respir J 18: 846-856 [Abstract] [Full Text]
Beenhouwer, D. O., Shapiro, S., Feldmesser, M., Casadevall, A., Scharff, M. D. (2001). Both Th1 and Th2 Cytokines Affect the Ability of Monoclonal Antibodies To Protect Mice against Cryptococcus neoformans. Infect. Immun. 69: 6445-6455 [Abstract] [Full Text]
Olszewski, M. A., Huffnagle, G. B., McDonald, R. A., Lindell, D. M., Moore, B. B., Cook, D. N., Toews, G. B. (2000). The Role of Macrophage Inflammatory Protein-1{alpha}/CCL3 in Regulation of T Cell-Mediated Immunity to Cryptococcus neoformans Infection. J. Immunol. 165: 6429-6436 [Abstract] [Full Text]
Kawakami, K., Koguchi, Y., Qureshi, M. H., Miyazato, A., Yara, S., Kinjo, Y., Iwakura, Y., Takeda, K., Akira, S., Kurimoto, M., Saito, A. (2000). IL-18 Contributes to Host Resistance Against Infection with Cryptococcus neoformans in Mice with Defective IL-12 Synthesis Through Induction of IFN-{gamma} Production by NK Cells. J. Immunol. 165: 941-947 [Abstract] [Full Text]
Buchanan, K. L., Doyle, H. A. (2000). Requirement for CD4+ T Lymphocytes in Host Resistance against Cryptococcus neoformans in the Central Nervous System of Immunized Mice. Infect. Immun. 68: 456-462 [Abstract] [Full Text]
Cano, L. E., Singer-Vermes, L. M., Costa, T. A., Mengel, J. O., Xidieh, C. F., Arruda, C., Andre, D. C., Vaz, C. A. C., Burger, E., Calich, V. L. G. (2000). Depletion of CD8+ T Cells In Vivo Impairs Host Defense of Mice Resistant and Susceptible to Pulmonary Paracoccidioidomycosis. Infect. Immun. 68: 352-359 [Abstract] [Full Text]
Lovchik, J. A., Wilder, J. A., Huffnagle, G. B., Riblet, R., Lyons, C. R., Lipscomb, M. F. (1999). Ig Heavy Chain Complex-Linked Genes Influence the Immune Response in a Murine Cryptococcal Infection. J. Immunol. 163: 3907-3913 [Abstract] [Full Text]
Mody, C. H., Wood, C. J., Syme, R. M., Spurrell, J. C.�L. (1999). The Cell Wall and Membrane of Cryptococcus neoformans Possess a Mitogen for Human T Lymphocytes. Infect. Immun. 67: 936-941 [Abstract] [Full Text]
Decken, K., Kohler, G., Palmer-Lehmann, K., Wunderlin, A., Mattner, F., Magram, J., Gately, M. K., Alber, G. (1998). Interleukin-12 Is Essential for a Protective Th1 Response in Mice Infected with Cryptococcus neoformans. Infect. Immun. 66: 4994-5000 [Abstract] [Full Text]
Izzo, A. A., Lovchik, J. A., Lipscomb, M. F. (1998). T and B Cell Independence of Endothelial Cell Adhesion Molecule Expression in Pulmonary Granulomatous Inflammation. Am. J. Respir. Cell Mol. Bio. 19: 588-597 [Abstract] [Full Text]
Yuan, R. R., Spira, G., Oh, J., Paizi, M., Casadevall, A., Scharff, M. D. (1998). Isotype Switching Increases Efficacy of Antibody Protection against Cryptococcus neoformans Infection in Mice. Infect. Immun. 66: 1057-1062 [Abstract] [Full Text]
Huffnagle, G. B., Boyd, M. B., Street, N. E., Lipscomb, M. F. (1998). IL-5 Is Required for Eosinophil Recruitment, Crystal Deposition, and Mononuclear Cell Recruitment During a Pulmonary Cryptococcus neoformans Infection in Genetically Susceptible Mice (C57BL/6). J. Immunol. 160: 2393-2400 [Abstract] [Full Text]