| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and CD8+ T Cells Restore Host Defenses Against Pneumocystis carinii in Mice Depleted of CD4+ T Cells1
,
,
*
Section of Pulmonary/Critical Care,
Gene Therapy Program, and
Section of Hematology/Oncology, Louisiana State University Medical Center School of Medicine, New Orleans, LA 70112
Host defenses against infection are profoundly compromised in
HIV-infected hosts due to progressive depletion of CD4+ T
lymphocytes and defective cell-mediated immunity. Although recent
advances in antiretroviral therapy can dramatically lower HIV viral
load, blood CD4+ T lymphocytes are not restored to normal
levels. Therefore, we investigated mechanisms of host defense other
than those involving CD4+ T lymphocytes against a common
HIV-related opportunistic infection, Pneumocystis
carinii (PC) pneumonia. Using CD4-depleted mice, which are
permissive for chronic PC infection, we show that up-regulation of
murine IFN-
by gene transfer into the lung tissue results in
clearance of PC from the lungs in the absence of CD4+
lymphocytes. This resolution of infection was associated with a
>4-fold increase in recruited CD8+ T lymphocytes and NK
cells into the lungs. The role of CD8+ T cells as effector
cells in this model was further confirmed by a lack of an effect of
IFN- gene transfer in scid mice or mice depleted of
both CD4+ and CD8+ T cells. Cytokine mRNA
analysis revealed that recruited, lung-derived CD8+ T cells
had greater expression of IFN- message in animals treated with the
IFN- gene. These results indicate that CD8+ T cells are
capable of clearing PC pneumonia in the absence of CD4+ T
cells and that this host defense function of CD8+ T cells,
as well as their cytokine repertoire, can be up-regulated through
cytokine gene transfer.
This article has been cited by other articles:
|
|
 |
|
  M. P. Nelson, A. E. Metz, S. Li, C. A. Lowell, and C. Steele The Absence of Hck, Fgr, and Lyn Tyrosine Kinases Augments Lung Innate Immune Responses to Pneumocystis murina Infect. Immun., May 1, 2009; 77(5): 1790 - 1797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Salat, J. Jelinek, J. Chmelar, and J. Kopecky Efficacy of Gamma Interferon and Specific Antibody for Treatment of Microsporidiosis Caused by Encephalitozoon cuniculi in SCID Mice Antimicrob. Agents Chemother., June 1, 2008; 52(6): 2169 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ruan, L. McKinley, M. Zheng, X. Rudner, A. D'Souza, J. K. Kolls, and J. E. Shellito Interleukin-12 and Host Defense against Murine Pneumocystis Pneumonia Infect. Immun., May 1, 2008; 76(5): 2130 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Empey, M. Hollifield, and B. A. Garvy Exogenous Heat-Killed Escherichia coli Improves Alveolar Macrophage Activity and Reduces Pneumocystis carinii Lung Burden in Infant Mice Infect. Immun., July 1, 2007; 75(7): 3382 - 3393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Millward, M. Caruso, I. L. Campbell, J. Gauldie, and T. Owens IFN-{gamma}-Induced Chemokines Synergize with Pertussis Toxin to Promote T Cell Entry to the Central Nervous System J. Immunol., June 15, 2007; 178(12): 8175 - 8182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Lasbury, S. Merali, P. J. Durant, D. Tschang, C. A. Ray, and C.-H. Lee Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia J. Biol. Chem., April 13, 2007; 282(15): 11009 - 11020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Rapaka, E. S. Goetzman, M. Zheng, J. Vockley, L. McKinley, J. K. Kolls, and C. Steele Enhanced Defense against Pneumocystis carinii Mediated by a Novel Dectin-1 Receptor Fc Fusion Protein J. Immunol., March 15, 2007; 178(6): 3702 - 3712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Bhagwat, F. Gigliotti, H. Xu, and T. W. Wright Contribution of T cell subsets to the pathophysiology of Pneumocystis-related immunorestitution disease Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1256 - L1266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Gigliotti, E. L. Crow, S. P. Bhagwat, and T. W. Wright Sensitized CD8+ T Cells Fail To Control Organism Burden but Accelerate the Onset of Lung Injury during Pneumocystis carinii Pneumonia Infect. Immun., November 1, 2006; 74(11): 6310 - 6316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. McKinley, A. J. Logar, F. McAllister, M. Zheng, C. Steele, and J. K. Kolls Regulatory T Cells Dampen Pulmonary Inflammation and Lung Injury in an Animal Model of Pneumocystis Pneumonia J. Immunol., November 1, 2006; 177(9): 6215 - 6226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Freeman, J. Davis, V. L. Anderson, W. Barson, D. N. Darnell, J. M. Puck, and S. M. Holland Pneumocystis jiroveci Infection in Patients With Hyper-Immunoglobulin E Syndrome Pediatrics, October 1, 2006; 118(4): e1271 - e1275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. McAllister, S. Ruan, C. Steele, M. Zheng, L. McKinley, L. Ulrich, L. Marrero, J. E. Shellito, and J. K. Kolls CXCR3 and IFN Protein-10 in Pneumocystis Pneumonia J. Immunol., August 1, 2006; 177(3): 1846 - 1854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Lasbury, P. J. Durant, C. A. Ray, D. Tschang, R. Schwendener, and C.-H. Lee Suppression of Alveolar Macrophage Apoptosis Prolongs Survival of Rats and Mice with Pneumocystis Pneumonia. J. Immunol., June 1, 2006; 176(11): 6443 - 6453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. McAllister, C. Steele, M. Zheng, J. E. Shellito, and J. K. Kolls In Vitro Effector Activity of Pneumocystis murina-Specific T-Cytotoxic-1 CD8+ T Cells: Role of Granulocyte-Macrophage Colony-Stimulating Factor Infect. Immun., November 1, 2005; 73(11): 7450 - 7457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, S. D. Tachado, N. Patel, J. Zhu, A. Imrich, P. Manfruelli, M. Cushion, T. B. Kinane, and H. Koziel Negative regulatory role of mannose receptors on human alveolar macrophage proinflammatory cytokine release in vitro J. Leukoc. Biol., September 1, 2005; 78(3): 665 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. N. Meissner, S. Swain, M. Tighe, A. Harmsen, and A. Harmsen Role of Type I IFNs in Pulmonary Complications of Pneumocystis murina Infection J. Immunol., May 1, 2005; 174(9): 5462 - 5471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Wright, G. S. Pryhuber, P. R. Chess, Z. Wang, R. H. Notter, and F. Gigliotti TNF Receptor Signaling Contributes to Chemokine Secretion, Inflammation, and Respiratory Deficits during Pneumocystis Pneumonia J. Immunol., February 15, 2004; 172(4): 2511 - 2521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Thullen, A. D. Ashbaugh, K. R. Daly, M. J. Linke, P. E. Steele, and P. D. Walzer Sensitized Splenocytes Result in Deleterious Cytokine Cascade and Hyperinflammatory Response in Rats with Pneumocystis Pneumonia despite the Presence of Corticosteroids Infect. Immun., February 1, 2004; 72(2): 757 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mc Allister, C. Steele, M. Zheng, E. Young, J. E. Shellito, L. Marrero, and J. K. Kolls T Cytotoxic-1 CD8+ T Cells Are Effector Cells against Pneumocystis in Mice J. Immunol., January 15, 2004; 172(2): 1132 - 1138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Steele, L. Marrero, S. Swain, A. G. Harmsen, M. Zheng, G. D. Brown, S. Gordon, J. E. Shellito, and J. K. Kolls Alveolar Macrophage-mediated Killing of Pneumocystis carinii f. sp. muris Involves Molecular Recognition by the Dectin-1 {beta}-Glucan Receptor J. Exp. Med., December 1, 2003; 198(11): 1677 - 1688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Swain, S. J. Lee, M. C. Nussenzweig, and A. G. Harmsen Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility to Pneumocystis carinii Infection In Vivo Infect. Immun., November 1, 2003; 71(11): 6213 - 6221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ruan, C. Tate, J. J. Lee, T. Ritter, J. K. Kolls, and J. E. Shellito Local Delivery of the Viral Interleukin-10 Gene Suppresses Tissue Inflammation in Murine Pneumocystis carinii Infection Infect. Immun., November 1, 2002; 70(11): 6107 - 6113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Gilmartin and H. Koziel Pneumocystis Carinii Pneumonia in Adult Non-HIV Disorders J Intensive Care Med, November 1, 2002; 17(6): 283 - 301. [Abstract] [PDF]
|
|
|
|
|
|
C. Steele, M. Zheng, E. Young, L. Marrero, J. E. Shellito, and J. K. Kolls Increased Host Resistance against Pneumocystis carinii Pneumonia in {gamma}{delta} T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+ T Cells Infect. Immun., September 1, 2002; 70(9): 5208 - 5215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Casciotti, K. H. Ely, M. E. Williams, and I. A. Khan CD8+-T-Cell Immunity against Toxoplasma gondii Can Be Induced but Not Maintained in Mice Lacking Conventional CD4+ T Cells Infect. Immun., February 1, 2002; 70(2): 434 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. BECK, M. J. ROSEN, and H. H. PEAVY Pulmonary Complications of HIV Infection . Report of the Fourth NHLBI Workshop Am. J. Respir. Crit. Care Med., December 1, 2001; 164(11): 2120 - 2126. [Full Text] [PDF]
|
|
|
|
|
|
A. J. Simpson, W. A. H. Wallace, M. E. Marsden, J. R. W. Govan, D. J. Porteous, C. Haslett, and J.-M. Sallenave Adenoviral Augmentation of Elafin Protects the Lung Against Acute Injury Mediated by Activated Neutrophils and Bacterial Infection J. Immunol., August 1, 2001; 167(3): 1778 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Xing, A. Zganiacz, J. Wang, and S. K. Sharma Enhanced Protection Against Fatal Mycobacterial Infection in SCID Beige Mice by Reshaping Innate Immunity with IFN-{{gamma}} Transgene J. Immunol., July 1, 2001; 167(1): 375 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Mansharamani, D. Balachandran, I. Vernovsky, R. Garland, and H. Koziel Peripheral Blood CD4 + T-Lymphocyte Counts During Pneumocystis carinii Pneumonia in Immunocompromised Patients Without HIV Infection Chest, September 1, 2000; 118(3): 712 - 720. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
