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Clinical and Vaccine Immunology, October 2008, p. 1616-1622, Vol. 15, No. 10
1071-412X/08/$08.00+0     doi:10.1128/CVI.00185-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis{triangledown} ,{dagger}

Marsha Feske,1,2,3 Rodolfo J. Nudelman,2 Miguel Medina,2 Justin Lew,3 Manisha Singh,2 Jacob Couturier,2 Edward A. Graviss,3 and Dorothy E. Lewis2*

University of Texas School of Public Health,1 Departments of Immunology,2 Pathology, Baylor College of Medicine, Houston, Texas3

Received 23 May 2008/ Returned for modification 27 June 2008/ Accepted 13 August 2008

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 (R2 = 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.

* Corresponding author. Mailing address: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Boulevard, Mail Route 0435, Galveston, TX 77555-0567. Phone: (409) 747-0240. Fax: (409) 772-6527. E-mail: dolewis{at}utmb.edu

{triangledown} Published ahead of print on 27 August 2008.

{dagger} Supplemental material for this article may be found at http://cvi.asm.org/.

Clinical and Vaccine Immunology, October 2008, p. 1616-1622, Vol. 15, No. 10
1071-412X/08/$08.00+0     doi:10.1128/CVI.00185-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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