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Journal of Virology, April 2002, p. 3646-3658, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3646-3658.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Decreased Frequency of Cytomegalovirus (CMV)-Specific CD4+ T Lymphocytes in Simian Immunodeficiency Virus-Infected Rhesus Macaques: Inverse Relationship with CMV Viremia

Amitinder Kaur,1* Corrina L. Hale,1 Bradley Noren,1 Nadine Kassis,1 Meredith A. Simon,2 and R. Paul Johnson1,3

Divisions of Immunology,1 Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,2 Infectious Disease Unit and Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 021293

Received 15 October 2001/ Accepted 10 January 2002

The frequency of cytomegalovirus (CMV)-specific CD4+ T lymphocytes was determined in CMV-seropositive rhesus macaques with or without simian immunodeficiency virus (SIV) infection by using the sensitive assays of intracellular cytokine staining and gamma interferon ELISPOT. Both techniques yielded 3- to 1,000-fold-higher frequencies of CMV-specific CD4+ T lymphocytes than traditional proliferative limiting dilution assays. The median frequency of CMV-specific CD4+ T lymphocytes in 23 CMV-seropositive SIV-negative macaques was 0.63% (range, 0.16 to 5.8%). The majority of CMV-specific CD4+ T lymphocytes were CD95pos and CD27lo but expressed variable levels of CD45RA. A significant reduction (P < 0.05) in the frequency of CMV-specific CD4+ T lymphocytes was observed in pathogenic SIV-infected macaques but not in macaques infected with live attenuated strains of SIV. CMV-specific CD4+ T lymphocytes were not detected in six of nine pathogenic SIV-infected rhesus macaques. CMV DNA was detected in the plasma of four of six of these macaques but in no animal with detectable CMV-specific CD4+ T lymphocytes. In pathogenic SIV-infected macaques, loss of CMV-specific CD4+ T lymphocytes was not predicted by the severity of CD4+ T lymphocytopenia. Neither was it predicted by the pre-SIV infection frequencies of CD45RAneg or CCR5pos CMV-specific CD4+ T lymphocytes. However, the magnitude of activation, as evidenced by the intensity of CD40L expression on CMV-specific CD4+ T lymphocytes pre-SIV infection, was three- to sevenfold greater in the two macaques that subsequently lost these cells after SIV infection than in the two macaques that retained CMV-specific CD4+ T lymphocytes post-SIV infection. Future longitudinal studies with these techniques will facilitate the study of CMV pathogenesis in AIDS.

* Corresponding author. Mailing address: Division of Immunology, New England Regional Primate Research Center, One Pinehill Dr., Southborough, MA 01772. Phone: (508) 624-8169. Fax: (508) 624-8172. E-mail: amitinder_kaur{at}hms.harvard.edu.

Journal of Virology, April 2002, p. 3646-3658, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3646-3658.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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