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Infection and Immunity, December 2000, p. 6826-6832, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Naive Human T Cells Develop into Th1 Effectors after Stimulation with Mycobacterium tuberculosis-Infected Macrophages or Recombinant Ag85 Proteins

Donna M. Russo,1,* Natalia Kozlova,1 David L. Lakey,2,dagger and Douglas Kernodle2

Meharry Medical College1 and Vanderbilt University School of Medicine, Veterans Affairs Medical Center,2 Nashville, Tennessee

Received 9 February 2000/Returned for modification 5 April 2000/Accepted 30 August 2000

Most studies of human T-cell responses in tuberculosis have focused on persons with either active disease or latent infection. Although this work has been critical in defining T-cell correlates of successful versus failed host containment, little is known about the development of Mycobacterium-specific T-cell responses in uninfected persons. To explore this issue, naive T cells from uninfected donors were sensitized in vitro with avirulent Mycobacterium tuberculosis-infected autologous macrophages. T-cell lines primed in this manner proliferated and produced cytokines after challenge with mycobacterial antigens. Of 11 such lines, 8 were high Th1 responders, 2 were low Th1 responders, and 1 was a Th2 responder. Furthermore, similar patterns and magnitudes of proliferative and cytokine responses were seen when Mycobacterium infection-primed lines were challenged with recombinant antigen 85 (Ag85) proteins. The addition of interleukin 12 (IL-12) during the initial sensitization increased the magnitude of Th1 responses; however, antibody to IL-12 did not eliminate Th1 responses, suggesting that additional factors contributed to the differentiation of these cells. Finally, in the presence of IL-12, recombinant Ag85B was able to prime naive T cells for Th1 responses upon challenge with Mycobacterium-infected macrophages or Ag85B. Therefore, under the appropriate conditions, priming with whole bacteria or a subunit antigen can stimulate Mycobacterium-specific Th1 effector cell development. Further definition of the antigens and conditions required to drive naive human T cells to differentiate into Th1 effectors should facilitate the development of an improved tuberculosis vaccine.

* Corresponding author. Present address: MCP Hahnemann School of Medicine, 2900 Queen Ln., Philadelphia, PA 19129. Phone: (215) 991-8556. Fax: (215) 848-2271. E-mail: donna.m.russo{at}drexel.edu.

dagger Present address: Center for Pulmonary and Infectious Diseases Control, University of Texas Health Center at Tyler, Tyler, TX 11937.

Infection and Immunity, December 2000, p. 6826-6832, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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