Article

Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis

University of Texas School of Public Health, Galveston, TX 77555-0567, USA.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.37). 09/2008; 15(10):1616-22. DOI: 10.1128/CVI.00185-08
Source: PubMed

ABSTRACT Children and immunocompromised adults are at an increased risk of tuberculosis (TB), but diagnosis is more challenging. Recently developed gamma interferon (IFN-gamma) release assays provide increased sensitivity and specificity for diagnosis of latent TB, but their use is not FDA approved in immunocompromised or pediatric populations. Both populations have reduced numbers of T cells, which are major producers of IFN-gamma. Interleukin 7 (IL-7), a survival cytokine, stabilizes IFN-gamma message and increases protein production. IL-7 was added to antigen-stimulated lymphocytes to improve IFN-gamma responses as measured by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Antigens used were tetanus toxoid (n = 10), p24 (from human immunodeficiency virus [HIV], n = 9), and TB peptides (n = 15). Keyhole limpet hemocyanin was used as a negative control, and phytohemagglutinin was the positive control. IL-7 improved antigen-specific responses to all antigens tested including tetanus toxoid, HIV type 1 p24, and TB peptides (ESAT-6 and CFP-10) with up to a 14-fold increase (mean = 3.8), as measured by ELISA. Increased IFN-gamma responses from controls, HIV-positive patients, and TB patients were statistically significant, with P values of <0.05, 0.01, and 0.05, respectively. ELISPOT assay results confirmed ELISA findings (P values of <0.01, 0.02, and 0.03, respectively), with a strong correlation between the two tests (R(2) = 0.82 to 0.99). Based on average background levels, IL-7 increased detection of IFN-gamma by 39% compared to the level with antigen alone. Increased production of IFN-gamma induced by IL-7 improves sensitivity of ELISA and ELISPOT assays for all antigens tested. Further enhancement of IFN-gamma-based assays might improve TB diagnosis in those populations at highest risk for TB.

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    • "One concern relating to the development of lateral flow based tests is the ability to detect markers that are produced in low amounts. It has been shown that cytokine responses can be enhanced by addition of cytokines such as IL-7 [45] and IL-12 [46] into cultures and through the delivery of the antigens using vectors such as the Bordetella pertusis adenylate cyclase vector [47], and other adjuvants [48]. Lateral flow tests using upconverting phospor technology were shown to detect IFN-γ in culture supernatants with sensitivity below 2 pg/ml and were more sensitive than ELISA in detecting Shistosoma circulating antigens [44]. "
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    • "It may also imply that the worth of testing candidate vaccines based on these antigens needs to be reassessed in certain populations. However, it has been shown that responses to TB antigens could be enhanced if antigens are delivered using vectors such as the Bordetella pertusis adenylate cyclase vector [43], use of other adjuvants [32] or the addition of IL-7 [44] and IL-12 [45] into cultures. It is not known if addition of cytokines might have improved upon the diagnostic ability of the antigens. "
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