Nature Medicine
4, 215 - 221 (1998)
doi:10.1038/nm0298-215
Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapyGuy Gorochov1, 6, Avidan U. Neumann1, 2, 5, Anne Kereveur1, Christophe Parizot1, Taisheng Li1, Christine Katlama3, Marina Karmochkine4, Gilles Raguin4, Brigitte Autran1
& Patrice Debré1
1Laboratoire d'Immunologie Cellulaire, CERVI, URA CNRS 625, Hôpital Pitié-Salpétrière, 83 Boulevard de l'Hôpital, 75013 Paris, France
2Department of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel
3Service de Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpétrière, 75013 Paris, France
4Service de Médecine Interne, Hôpital de la Croix Saint-Simon, 75020 Paris, France A.U.N. and G.G. contributed equally to this work. Information regarding mathematical analysis should be obtained from A.U.N.; neumann@macs.biu.ac.il Correspondence should be addressed to G.G.; guy.gorochov@psl.ap-hop-paris.fr The T-cell antigen receptor (TCR) repertoire was studied longitudinally by analyzing the varying lengths of the beta chain CDR3 hypervariable region during the course of HIV-1 infection and following combination antiretroviral therapy. Drastic restrictions in CD8+ T-cell repertoire usage were found at all stages of natural progression and persisted during the first six months of treatment. In contrast, significant CD4+ T-cell repertoire perturbations were not found in early stages of infection but correlated with progression to AIDS. Out of ten patients presenting with pretreatment perturbations, normalization of the CD4+ repertoire was observed in eight good responders, but not in two cases of unsuccessful therapy. These results indicate that, besides CD4+ cell count rise, an efficient control of HIV replication may allow qualitative modifications of the CD4+ repertoire balance.
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