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Infection and Immunity, April 2003, p. 1929-1937, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1929-1937.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Apa Protein of Mycobacterium tuberculosis Stimulates Gamma Interferon-Secreting CD4⁺ and CD8⁺ T Cells from Purified Protein Derivative-Positive Individuals and Affords Protection in a Guinea Pig Model

Priti Kumar,¹ Rama Rao Amara,^1, Vijay Kumar Challu,² Vineet Kumar Chadda,² and Vijaya Satchidanandam^1*

Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012,¹ National Tuberculosis Institute, Bangalore 560003, India²

Received 15 October 2002/ Returned for modification 10 December 2002/ Accepted 27 December 2002

The search to identify Mycobacterium tuberculosis antigens capable of conferring protective immunity against tuberculosis has received a boost owing to the resurgence of tuberculosis over the past two decades. It has long been recognized that lymphoid cells are required for protection against M. tuberculosis. While traditionally the CD4⁺ populations of T cells were believed to predominantly serve this protective function, a pivotal role for CD8⁺ T cells in this task has been increasingly appreciated. We show that the 50- to 55-kDa Apa protein, specified by the Rv1860 gene of M. tuberculosis, can elicit both lymphoproliferative response and gamma interferon (IFN-) production from peripheral blood mononuclear cells (PBMC) of purified protein derivative (PPD)-positive individuals, with significant differences recorded in the levels of responsiveness between PPD-positive healthy controls and pulmonary tuberculosis patients. Flow cytometric analysis of whole blood stimulated with the recombinant Apa protein revealed a sizeable proportion of CD8⁺ T cells in addition to CD4⁺ T cells contributing to IFN- secretion. PBMC responding to the Apa protein produced no interleukin-4, revealing a Th1 phenotype. A DNA vaccine and a poxvirus recombinant expressing the Apa protein were constructed and tested for their ability to protect immunized guinea pigs against a challenge dose of virulent M. tuberculosis. Although the DNA vaccine afforded little protection, the poxvirus recombinant boost after DNA vaccine priming conferred a significant level of protective immunity, bringing about a considerable reduction in mycobacterial counts from the challenge bacilli in spleens of immunized guinea pigs, a result comparable to that achieved by BCG vaccination.

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* Corresponding author. Mailing address: Room 254A, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India. Phone: 91-80-3942685. Fax: 91-80-3942685. E-mail: vijaya{at}mcbl.iisc.ernet.in.

Editor: W. A. Petri, Jr.

Present address: Department of Microbiology and Immunology, Yerkes Primate Research Centre, Emory University, Atlanta, GA 30329.

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Infection and Immunity, April 2003, p. 1929-1937, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.1929-1937.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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