Restoration of cellular immunity against tuberculosis in patients coinfected with HIV-1 and tuberculosis with effective antiretroviral therapy: Assessment by determination of CD69 expression on T cells after tuberculin stimulation
Journal
Journal of Acquired Immune Deficiency Syndromes
Journal Volume
25
Journal Issue
3
Pages
212-220
Date Issued
2000
Author(s)
Abstract
Whether immunity against opportunistic pathogens can be fully restored by control of HIV-1 replication remains open to question. This longitudinal study was conducted to measure anti-tuberculosis (TB) cellular immunity in 13 HIV-1/TB-coinfected patients effectively treated by highly active antiretroviral therapy (HAART) in a period of 12 months. In this study, anti-TB cellular immunity was assessed by determining the frequencies of CD 69 expression on CD4+ and CD8+ T cells in response to purified protein derivative (PPD) stimulation (abbreviated as %CD4+CD69 to PPD and %CD8+CD69 to PPD). Here, we show that %CD4+CD69 to PPD correlated with the results of tuberculin skin tests and interferon-γ (IFN-γ) production from PPD-stimulated CD4+ T cells, and %CD8+CD69 to PPD also correlated with CD8+ T cell-mediated PPD-specific cytolysis. In overall analysis for these 13 patients, both %CD4+CD69 to PPD and %CD8+CD69 to PPD increased significantly during the 12 months (p = .003 and p < .001, respectively). However, we found %CD4+CD69 to PPD or %CD8+CD69 to PPD failed to increase substantially in some patients (i.e., immunologic nonresponders). A significantly higher proportion of patients whose baseline CD4+ count was <50 cells/mm3 were considered to be CD4+ nonresponders compared with those whose baseline CD4+ count was >50 cells/mm3. Furthermore, baseline CD4+ cell count in nonresponders is significantly lower than that in responders, although the effectiveness of HAART did not differ between them. Our results indicate that PPD-specific frequencies of CD69 expression may be used as surrogate markers of anti-TB cellular immunity. By this method, we show that full reconstitution of anti-TB cellular immunity in HIV-1/TB coinfected patients may not necessarily be achieved by "successful" HAART and may be influenced by the baseline immune status when HAART is started. These data suggest that the decision to discontinue secondary prophylaxis for opportunistic infections should be cautiously made, even when the CD4+ cell count has significantly increased.
SDGs
Other Subjects
antiretrovirus agent; CD4 antigen; CD69 antigen; CD8 antigen; gamma interferon; tuberculin; acquired immune deficiency syndrome; adult; AIDS related complex; article; cell count; cellular immunity; clinical article; controlled study; cytolysis; drug efficacy; human; Human immunodeficiency virus; Human immunodeficiency virus infection; immunostimulation; interferon production; opportunistic infection; priority journal; prophylaxis; protein expression; superinfection; tuberculin test; tuberculosis
Publisher
Lippincott Williams and Wilkins
Type
journal article