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Journal of Virology, September 1999, p. 7108-7116, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8+ Responses in HIV Type 1-Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy

Marc Dalod,1,* Marion Dupuis,1 Jean-Christophe Deschemin,1 Didier Sicard,2 Dominique Salmon,2 Jean-Francois Delfraissy,3 Alain Venet,1 Martine Sinet,1 and Jean-Gerard Guillet1

Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, Unité 445, Institut National de la Santé et de la Recherche Médicale, Institut Cochin de Génétique Moléculaire, Université René Descartes,1 and Département de Médecine Interne, Hôpital Cochin,2 Paris 75014, and Unité 292, Institut National de la Santé et de la Recherche Médicale, Hôpital de Bicêtre, Le Kremlin Bicêtre 94276,3 France

Received 25 January 1999/Accepted 20 May 1999

The ex vivo antiviral CD8+ repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4+ T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8+ responses and the CD4+ counts or virus load. In contrast, the polyclonality of anti-HIV CD8+ responses was positively correlated with the CD4+ counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4+ counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8+ responses in two patients with stable CD4+ counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8+ T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8+ responses at all stages of HIV infection and suggest that the CD8+ hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8+ T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8+ responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8+ responses may occur with depletion of CD4+ T cells, but this could be restored by highly active antiretroviral treatment.

* Corresponding author. Mailing address: INSERM U445, ICGM, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. Phone: 33 (0)1 44 07 18 21. Fax: 33 (0)1 44 07 14 25. E-mail: dalod{at}icgm.cochin.inserm.fr.

Journal of Virology, September 1999, p. 7108-7116, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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