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Infection and Immunity, September 2002, p. 5208-5215, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5208-5215.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Increased Host Resistance against Pneumocystis carinii Pneumonia in {gamma}{delta} T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+ T Cells

Chad Steele, Mingquan Zheng, Erana Young, Luis Marrero, Judd E. Shellito, and Jay K. Kolls*

Section of Pulmonary and Critical Care and Gene Therapy Program, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Received 28 March 2002/ Returned for modification 9 May 2002/ Accepted 2 June 2002

Although a clear relationship between {alpha}ß T-cell receptor-positive ({alpha}ß-TCR+) CD4+ T cells and susceptibility to Pneumocystis carinii infection exists, the role of other T-cell subsets is less clearly defined. Previous studies have shown that {gamma}{delta}-TCR+ T cells infiltrate into the lung during P. carinii pneumonia. Therefore, the present study examined the role of {gamma}{delta}-TCR+ T cells in host defense against P. carinii pneumonia. C57BL/6 (control) and B6.129P2-Tcrdtm1Mom ({gamma}{delta}-TCR+ T-cell-deficient) mice were inoculated intratracheally with P. carinii. At specific time points, mice were sacrificed and analyzed for P. carinii burden, T-cell subsets, and cytokine levels in lung tissue. Analysis of P. carinii burden showed a more rapid and complete resolution of infection in {gamma}{delta}-TCR+ T-cell-deficient mice than in C57BL/6 controls. This augmented resolution was associated with elevated gamma interferon (IFN-{gamma}) levels in bronchoalveolar lavage fluid predominantly produced by CD8+ T cells, as well as an increased recruitment of CD8+ T cells in general. In separate experiments, neutralization of IFN-{gamma} or depletion of CD8+ T cells early during infection abolished the augmented resolution previously observed in {gamma}{delta}-TCR+ T-cell-deficient mice. These results show that the presence of {gamma}{delta}-TCR+ T cells modulates host susceptibility to P. carinii pneumonia through interactions with pulmonary CD8+ T cells and tissue production of IFN-{gamma}.

* Corresponding author. Mailing address: Louisiana State University Health Sciences Center, Gene Therapy Program, Clinical Sciences Research Building, 533 Bolivar St., Box 6-16, New Orleans, LA 70112. Phone: (504) 568-6152. Fax: (504) 568-8500. E-mail: jkolls{at}lsuhsc.edu.

Editor: T. R. Kozel

Infection and Immunity, September 2002, p. 5208-5215, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5208-5215.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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