Abstract
The mycolyl transferase antigen 85 complex is a major secreted protein family from mycobacterial culture filtrate, demonstrating powerful T cell stimulatory properties in most HIV-negative, tuberculin-positive volunteers with latent M.tuberculosis infection and only weak responses in HIV-negative tuberculosis patients. Here, we have analyzed T cell reactivity against PPD and Ag85 in HIV-infected individuals, without or with clinical symptoms of tuberculosis, and in AIDS patients with disease caused by nontuberculous mycobacteria. Whereas responses to PPD were not significantly different in HIV-negative and HIV-positive tuberculin-positive volunteers, responses to Ag85 were significantly decreased in the HIV-positive (CDC-A and CDC-B) group. Tuberculosis patients demonstrated low T cell reactivity against Ag85, irrespective of HIV infection, and finally AIDS patients suffering from NTM infections were completely nonreactive to Ag85. A one-year follow-up of twelve HIV-positive tuberculin-positive individuals indicated a decreased reactivity against Ag85 in patients developing clinical tuberculosis, highlighting the protective potential of this antigen.
Highlights
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), remains the largest single infectious cause of death globally
It is estimated that more than one third of HIV-positive individuals are coinfected with M. tuberculosis, and approximately 12% of AIDS deaths are due to TB [3, 28]
Despite the limited number of subjects in this followup, our results strongly suggest a protective role of Ag85-specific T cell responses in the control of M. tuberculosis infection
Summary
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis (TB), remains the largest single infectious cause of death globally. About one third of the world population is infected with M. tuberculosis, and in 2008 an estimated 1.3 million people died of tuberculosis and an estimated 9.3 million people developed the disease worldwide (http://www.who.int/mediacentre/factsheets/fs104/ en/index.html). Administration for many decades of the attenuated strain of M. bovis BCG (Bacillus CalmetteGuerin) as a vaccine—which in 2000 covered 86% of the world population [1]—has not been able to eradicate this poverty-related sickness. At least one third of the more than 30 million people infected with the human immunodeficiency virus HIV worldwide are infected with M. tuberculosis. HIVpositive subjects are at increased risk to reactivate a latent M. tuberculosis infection, even when CD4+ counts are still relatively unaffected. Tuberculosis coinfected subjects [3, 4]. In 2008, there were 1.4 million HIV-positive tuberculosis patients globally and 500,000 people died of HIV-associated TB http://www .who.int/tb/challenges/hiv/factsheet hivtb 2009update.pdf
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