Abstract

. Pneumocystis carinii pneumonia (PcP) is an infection that occurs widely in hosts with suppressed immune systems. It is clear that CD4+ cells play a central role in host defense against this opportunistic pathogen. However, it is likely that redundancy in some mechanisms of cellular immune defense occurs in the host, specifically in the CD8+ lineage of T-cells. Since HIV-infected individuals have reduced CD4+ cell numbers, but increased or sustained levels of CD8+ T cells, it is proposed that by stimulating the anti-Pc and immunomodulatory capacities of the CD8+ cells in CD4+-depleted PcP-infected hosts, the outcome of PcP-infected individuals should improve. To test these hypotheses, the following specific aims are proposed: (1) determine whether cytokine products of CD8+ T cells activate alveolar macrophages for phagocytosis and killing of Pc in vitro; (2) determine whether CD8+ T cells are cytotoxic towards Pc alone or in association with alveolar macrophages in vitro; (3) determine ability of immunization with Pc to increase CD8+ T cell responses and decrease infection in vivo; and (4) determine the ability of transfer of Pc-elicited CD8+ T cells to modulate infection in vivo.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057011-03
Application #
2901269
Study Section
AIDS and Related Research Study Section 5 (ARRE)
Project Start
1997-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Atochina, Elena N; Gow, Andrew J; Beck, James M et al. (2004) Delayed clearance of pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice. J Infect Dis 189:1528-39
Luikart, Sharon; Masri, Mohammed; Wahl, Dan et al. (2002) Urokinase is required for the formation of mactinin, an alpha-actinin fragment that promotes monocyte/macrophage maturation. Biochim Biophys Acta 1591:99-107
Atochina, E N; Beck, J M; Scanlon, S T et al. (2001) Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D. J Lab Clin Med 137:429-39
Cushion, M T; Beck, J M (2001) Summary of Pneumocystis research presented at the 7th International Workshop on Opportunistic Protists. J Eukaryot Microbiol Suppl:101S-105S
Atochina, E N; Beers, M F; Scanlon, S T et al. (2000) P. carinii induces selective alterations in component expression and biophysical activity of lung surfactant. Am J Physiol Lung Cell Mol Physiol 278:L599-609
Beck, J M (2000) Pneumocystis carinii and geographic clustering: evidence for transmission of infection. Am J Respir Crit Care Med 162:1605-6
Paine 3rd, R; Preston, A M; Wilcoxen, S et al. (2000) Granulocyte-macrophage colony-stimulating factor in the innate immune response to Pneumocystis carinii pneumonia in mice. J Immunol 164:2602-9
Beck, J M; Preston, A M; Gyetko, M R (1999) Urokinase-type plasminogen activator in inflammatory cell recruitment and host defense against Pneumocystis carinii in mice. Infect Immun 67:879-84
Beers, M F; Atochina, E N; Preston, A M et al. (1999) Inhibition of lung surfactant protein B expression during Pneumocystis carinii pneumonia in mice. J Lab Clin Med 133:423-33
Rudmann, D G; Preston, A M; Moore, M W et al. (1998) Susceptibility to Pneumocystis carinii in mice is dependent on simultaneous deletion of IFN-gamma and type 1 and 2 TNF receptor genes. J Immunol 161:360-6

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