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Infection and Immunity, June 2005, p. 3577-3586, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3577-3586.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Gamma Interferon-Induced T-Cell Loss in Virulent Mycobacterium avium Infection

Manuela Flórido,1 John E. Pearl,3 Alejandra Solache,3 Margarida Borges,1 Laura Haynes,3 Andrea M. Cooper,3 and Rui Appelberg1,2*

Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology,1 Instituto de Ciências Biomédicas de Abel Salazar, University of Porto, Porto, Portugal,2 Trudeau Institute, Saranac Lake, New York3

Received 9 September 2004/ Returned for modification 2 December 2004/ Accepted 11 January 2005

Infection by virulent Mycobacterium avium caused progressive severe lymphopenia in C57BL/6 mice due to increased apoptosis rates. T-cell depletion did not occur in gamma interferon (IFN-{gamma})-deficient mice which showed increased T-cell numbers and proliferation; in contrast, deficiency in nitric oxide synthase 2 did not prevent T-cell loss. Although T-cell loss was IFN-{gamma} dependent, expression of the IFN-{gamma} receptor on T cells was not required for depletion. Similarly, while T-cell loss was optimal if the T cells expressed IFN-{gamma}, CD8+ T-cell depletion could occur in the absence of T-cell-derived IFN-{gamma}. Depletion did not require that the T cells be specific for mycobacterial antigen and was not affected by deficiencies in the tumor necrosis factor receptors p55 or p75, the Fas receptor (CD95), or the respiratory burst enzymes or by forced expression of bcl-2 in hematopoietic cells.

* Corresponding author. Mailing address: Laboratory of Microbiology and Immunology of infection, Institute for Molecular and Cell Biology, University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. Phone: 351 226074952. Fax: 351 226099157. E-mail: rappelb{at}ibmc.up.pt.

Editor: V. J. DiRita

Infection and Immunity, June 2005, p. 3577-3586, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3577-3586.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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