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Clinical and Vaccine Immunology, September 2008, p. 1398-1409, Vol. 15, No. 9
1071-412X/08/$08.00+0 doi:10.1128/CVI.00479-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
In Vitro Cell-Mediated Immune Responses of Human Immunodeficiency Virus-Infected and -Uninfected Individuals to Whole Cytomegalovirus Antigens and Their Subunits
A. Weinberg,1*
J. Spritzler,2
M. Nokta,3,
R. Schrier,4
A. Landay,5
D. Brown,1,
R. Pollard,3,
for the ACTG CMV Task Force
University of Colorado School of Medicine, Denver, Colorado,1 Harvard School of Public Health, Boston, Massachusetts,2 University of Texas Medical Branch, Galveston, Texas,3 University of California, San Diego, California,4 Rush Medical School, Chicago, Illinois5
Received 6 December 2007/ Returned for modification 8 February 2008/ Accepted 13 June 2008
The aim of this study was to optimize the ability to detect cytomegalovirus (CMV)-specfic cell-mediated immunity (CMI) in human immunodeficiency virus (HIV)-infected individuals by comparing different assays (the lymphocyte proliferation assay [LPA] and assays for gamma interferon [IFN-
] and interleukin-2 [IL-2] production) and CMV antigenic preparations. Thresholds discriminating positive from negative CMI results were developed with specimens from 36 CMV-seropositive and 21 CMV-seronegative healthy individuals. The analysis showed that the CMI elicited by any of the four CMV whole lysates tested in this study tended to be more robust and sensitive than the responses to the subunit antigens gB and pp65. LPA and inducible IFN- but not IL-2 were highly sensitive measures of CMV-specific CMI in HIV-infected and -uninfected individuals. The ability to detect CMV-specific LPA or IFN- responses in HIV-infected individuals significantly increased with higher CD4 cell numbers. Nevertheless, the proportion of HIV-infected subjects with CD4 counts of 
500 cells/µl who had a detectable CMV-specific CMI remained significantly lower than that of healthy adults. The ability to detect CMV-specific CMI in HIV-infected individuals decreased with higher levels of HIV replication, with discriminative thresholds of 103 to 104 HIV RNA copies/ml of plasma, for LPA or inducible IFN- production elicited by different antigens. The LPA responses obtained with CMV whole lysate and phytohemagglutinin were significantly correlated in HIV-infected subjects but not uninfected controls, indicating a novel characteristic of the CMI defect caused by HIV. The intrasubject variabilities of the CMV-specific CMI were similar in HIV-infected and -uninfected individuals. These data show that LPA and the inducible IFN- production elicited by CMV whole lysates may be used to assess modifications of the immune competency of HIV-infected individuals.
* Corresponding author. Mailing address: UCHSC, 4200 East Ninth Ave., Denver, CO 80262. Phone: (303) 315-4624. Fax: (303) 315-1787. E-mail: Adriana.Weinberg{at}uchsc.edu
Published ahead of print on 25 June 2008.
Present address: National Institutes of Health, Bethesda, MD.
Present address: University of Auckland, Auckland, New Zealand.
Present address: University of California, Davis, CA.
Clinical and Vaccine Immunology, September 2008, p. 1398-1409, Vol. 15, No. 9
1071-412X/08/$08.00+0 doi:10.1128/CVI.00479-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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