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Naive Human T Cells Develop into Th1 Effectors after Stimulation with Mycobacterium tuberculosis-Infected Macrophages or Recombinant Ag85 Proteins
Journal article   Open access   Peer reviewed

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

Donna M Russo, Natalia Kozlova, David L Lakey and Douglas Kernodle
Infection and immunity, v 68(12), pp 6826-6832
Dec 2000
DOI: https://doi.org/10.1128/IAI.68.12.6826-6832.2000
PMID: 11083801
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/IAI.68.12.6826-6832.2000View
Published, Version of Record (VoR) Open

Abstract

Microbial Immunity and Vaccines
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
Infectious Diseases
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