Naive human T cells develop into Th1 effectors after stimulation with Mycobacterium tuberculosis-infected macrophages or recombinant Ag85 proteins.

Abstract

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.

• Authors: D M Russo, N Kozlova, D L Lakey, D Kernodle
• Journal: Infection and immunity (Infect Immun) Vol. 68 Issue 12 Pg. 6826-32 (Dec 2000) ISSN: 0019-9567 [Print] United States
• PMID: 11083801 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antigens, Bacterial
• Recombinant Proteins
• antigen 85, Mycobacterium bovis
• Interleukin-12
• Interleukin-4
• Interferon-gamma

Topics

• Antigens, Bacterial (immunology)
• Cell Line
• Humans
• Immunization
• Interferon-gamma (biosynthesis)
• Interleukin-12 (physiology)
• Interleukin-4 (biosynthesis)
• Macrophages (microbiology, physiology)
• Mycobacterium tuberculosis (immunology)
• Recombinant Proteins (immunology)
• Th1 Cells (immunology)