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

Hsieh, Shu‐Ching; Hung, Chien‐Ching; Pan, Sung‐Ching; Wang, Jann-Tay; Tsai, Hsing-Chun; Chen, Mao-Yuan; Chang, Shan-Chwen

doi:10.1097/00126334-200011010-00002

Cited by 32 publications

(17 citation statements)

References 34 publications

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“…In fact, although it has been demonstrated that HAART can induce restoration of in vitro response to mycobacterial antigen [25], studies conducted in patients co-infected with HIV and tuberculosis suggest that recovery of cellular immunity against tuberculosis may be delayed, incomplete or absent in some individuals who have a good immunological and virological response to antiretroviral therapy [26,27], particularly when HAART is started at low CD4 lymphocytes count [24]. However, when interpreting data on CD4 lymphocyte counts at the time of diagnosis of tuberculosis it should be taken into account that active tuberculosis itself can cause immunosuppression, as suggested by the transient decrease in CD4 lymphocytes observed in a significant proportion of HIV-negative patients with tuberculosis [28,29].…”

Section: Discussionmentioning

confidence: 99%

Tuberculosis in HIV‐infected persons in the context of wide availability of highly active antiretroviral therapy

et al. 2004

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Highly active antiretroviral therapy (HAART) greatly reduces the risk of developing tuberculosis for HIV‐infected persons. Nonetheless, HIV‐associated tuberculosis continues to occur in countries where HAART is widely used.To identify the characteristics of HIV‐infected persons who develop tuberculosis in the context of the availability of HAART, the current authors analysed data taken from 271 patients diagnosed, in Italy, during 1999–2000. These patients represent 0.7% of the 40,413 HIV‐infected patients cared for in the clinical units participating in this current study.From the data it was observed that 20 patients (7.4%) had a previous episode of tuberculosis whose treatment was not completed. Eighty-one patients (29.9%) were diagnosed with HIV at tuberculosis diagnosis, 108 (39.8%) were aware of their HIV status but were not on antiretroviral treatment and 82 (30.3%) were on antiretroviral treatment. Patients on antiretroviral treatment were significantly less immunosuppressed than patients with HIV diagnosed concurrently with tuberculosis, or other patients not on antiretrovirals (median CD4 lymphocytes count: 220 cells·mm−3versus100 cells·mm−3, and 109 cells·mm−3, respectively). No significant differences in clinical presentation of tuberculosis according to antiretroviral therapy status were recorded.Failure of tuberculosis control interventions (e.g.noncompletion of treatment) and of HIV care (delayed diagnosis of HIV infection and suboptimal uptake of therapy) may contribute to continuing occurrence of HIV‐associated tuberculosis in a country where highly active antiretroviral therapy is largely available. However, a significant proportion of cases occur in patients who are on antiretroviral treatment.

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Section: Discussionmentioning

confidence: 99%

Tuberculosis in HIV‐infected persons in the context of wide availability of highly active antiretroviral therapy

et al. 2004

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“…Expression of CD69 on lymphocytes has been shown to be associated with cellular immune function in patients with a variety of other conditions (6,17,22,25). In addition, other rapid assays have been found to be useful in determining the cellular immune response in patients with other granulomatous conditions.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Whole-Blood Analysis of Cellular Immunity in Patients with Active Coccidioidomycosis by Using the Antigen Preparation T27K

Ampel

Kramer

et al. 2002

Clin Vaccine Immunol

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Measurement of cellular immunity in human coccidioidomycosis has important diagnostic and prognostic implications. The coccidioidin skin test has been the standard for the measurement of this, but it is not available in the United States. We examined the utility of measuring surface expression of CD69 on T lymphocytes in whole blood incubated with the coccidioidal antigen preparation T27K as an alternative to the skin test. Seventy donors with active coccidioidomycosis were studied. The mean fluorescent intensity (MFI) of CD69 expression on CD3 lymphocytes in response to T27K was 28.61 ؎ 1.77, significantly greater than the control response of 11.45 ؎ 0.78 (P < 0.001). The MFI CD69 response to T27K above that for the control (MFI CD69 above control) was 6.35 ؎ 2.18 for seven subjects with disseminated coccidioidomycosis who were studied within 5 months of diagnosis. This was significantly below the value of 20.17 ؎ 3.17 for 18 subjects with pulmonary coccidioidomycosis studied within 5 months of diagnosis and the value of 19.58 ؎ 2.91 for 27 subjects with disseminated coccidioidomycosis studied after 5 months of diagnosis (for both, P < 0.05). There was an inverse correlation between coccidioidal clinical score and MFI CD69 above control for all 34 subjects with disseminated coccidioidomycosis (r ‫؍‬ 0.362; P ‫؍‬ 0.036) but not for the 36 subjects with pulmonary disease (r < 0.001; P ‫؍‬ 0.993). Among 30 subjects for whom data were available, there was a highly significant association between the MFI CD69 above control and the supernatant concentrations of gamma interferon, interleukin-2 (IL-2), and tumor necrosis factor alpha (for all, P < 0.001), but not for IL-4, IL-5, or IL-10. These data indicate that in vitro assessment of CD69 expression on T lymphocytes by using T27K may be a useful measure of cellular immune response among subjects with active coccidioidomycosis.

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“…A significantly higher level of expression of CD69 was found in patients with TB 8 months after they started treatment compared to that in healthy controls (26). Furthermore, in patients coinfected with HIV type 1 and M. tuberculosis, the expression of CD69 correlated with the results of TST and IFN-␥ production in PPD-stimulated CD4 T lymphocytes (15). Because little is known about CD69 antigen expression on CD4 T lymphocytes after in vitro tuberculin stimulation in patients with proven active TB before treatment and individuals with clinically inactive TB and a history of a previous episode of TB, we designed a study to evaluate the expression of CD69 on CD4 T lymphocytes using flow cytometry.…”

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confidence: 86%

CD69 Expression on CD4⁺T Lymphocytes after In Vitro Stimulation with Tuberculin Is an Indicator of Immune Sensitization againstMycobacterium tuberculosisAntigens

Avgustin

Kotnik

Škoberne

et al. 2005

Clin Vaccine Immunol

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The expression of the CD69 antigen on CD4 T lymphocytes after in vitro stimulation with purified protein derivative (2 tuberculin units) was used to evaluate the tuberculin reactivities of 52 individuals from four experimental groups: Mycobacterium bovis BCG-vaccinated healthy individuals with a negative tuberculin skin test (TST) result (group A), BCG-vaccinated healthy individuals with a positive TST result (group B), patients with active tuberculosis (TB) before treatment (group C), and individuals with clinically inactive TB who had previously completed a prescribed course of chemotherapy (group D). The expression of CD69 on CD4 T lymphocytes was significantly higher in patients with active TB (16.2% ؎ 7.3%), individuals with clinically inactive TB (10.5% ؎ 7.4%), and healthy individuals with a positive TST result (15.5% ؎ 7.2%) than in healthy individuals with a negative TST result (3.8% ؎ 4.3%) (P < 0.005). We confirmed the correlation between CD69 antigen expression on T lymphocytes after stimulation with tuberculin and the TST induration diameter (Spearman rho ‫؍‬ 0.783; P < 0.001), an assay for gamma interferon (the Quantiferon-TB assay; Spearman rho ‫؍‬ 0.613; P < 0.001), and the lymphocyte BLAST transformation test (Spearman rho ‫؍‬ 0.537; P < 0.001). Our results demonstrate the usefulness of the determination of CD69 on CD4 T lymphocytes after in vitro stimulation with tuberculin as a rapid indicator of immune sensitization against Mycobacterium tuberculosis.The fast, early, and accurate diagnosis of Mycobacterium tuberculosis infection is a very important element of global health measures for the control of tuberculosis (TB). The identification of individuals with latent M. tuberculosis infection (LTBI) who will benefit from treatment is crucial to the goal of TB elimination (1, 2). Since the immune response to mycobacterial infection is predominantly cellular (11), assessment of whether a patient's T cells have been exposed to and sensitized by antigens specific to M. tuberculosis provides an approach to diagnosis (4). Delayed-type hypersensitivity skin testing by the tuberculin skin test (TST) with purified protein derivate (PPD) is the standard method of screening for TB and has been a convenient, cost-effective method for assessment of the cell-mediated immune response to a tuberculin. Although TST has been the "gold standard" for diagnostic screening and the detection of new or asymptomatic TB, it has a number of drawbacks, including the need for a return visit to allow reading of the results, problems with interpretation of the test results due to cross-reactivity with other mycobacterial species, the booster effect, false-negative results due to intercurrent immunosuppression, and the variability inherent in its application and reading (16). In addition, it is imprecise and can give only a partial assessment of the interrelationships among M. tuberculosis, host macrophages, and the surrounding cellular components of the immune system, particularly CD4 T lymphocytes (5, 22). Different types of...

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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

Cited by 32 publications

References 34 publications

Tuberculosis in HIV‐infected persons in the context of wide availability of highly active antiretroviral therapy

Tuberculosis in HIV‐infected persons in the context of wide availability of highly active antiretroviral therapy

In Vitro Whole-Blood Analysis of Cellular Immunity in Patients with Active Coccidioidomycosis by Using the Antigen Preparation T27K

CD69 Expression on CD4⁺T Lymphocytes after In Vitro Stimulation with Tuberculin Is an Indicator of Immune Sensitization againstMycobacterium tuberculosisAntigens

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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

Cited by 32 publications

References 34 publications

Tuberculosis in HIV‐infected persons in the context of wide availability of highly active antiretroviral therapy

Tuberculosis in HIV‐infected persons in the context of wide availability of highly active antiretroviral therapy

In Vitro Whole-Blood Analysis of Cellular Immunity in Patients with Active Coccidioidomycosis by Using the Antigen Preparation T27K

CD69 Expression on CD4+T Lymphocytes after In Vitro Stimulation with Tuberculin Is an Indicator of Immune Sensitization againstMycobacterium tuberculosisAntigens

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CD69 Expression on CD4⁺T Lymphocytes after In Vitro Stimulation with Tuberculin Is an Indicator of Immune Sensitization againstMycobacterium tuberculosisAntigens