Following on the heels of yesterday’s post, a study has just been published by the journal AIDS that echoes the same themes. The researchers, led by Victor Appay, find that depletion of naïve CD4 and CD8 T cells represents the major parallel between HIV infection and aging and, like Beth Jamieson’s group, they note that the effects are additive. The researchers also report that immune responses to another chronic infection – CMV – are associated with reduced naïve T cell reconstitution in people with HIV on antiretroviral therapy, consistent with the idea that chronic infections can place a drain on naïve T cell resources (CMV infection has also been associated with reduced naïve T cell levels in individuals not infected with HIV). Additionally, Appay and colleagues look at markers of T cell senescence in HIV and aging, but find that the parallels are not as clear as those documented for naïve T cells.
AIDS. 2011 Mar 15. [Epub ahead of print]
Appay V, Fastenackels S, Katlama C, Ait-Mohand H, Schneider L, Guihot A, Keller M, Grubeck-Loebenstein B, Simon A, Lambotte O, Hunt PW, Deeks SG, Costagliola D, Autran B, Sauce D.
a INSERM UMR S 945, Infections and Immunity, Avenir Group, Université Pierre et Marie Curie-Paris6, Hôpital Pitié-Salpêtrière, 75013 Paris, France b AP-HP, Groupe hospitalier Pitié-Salpêtrière, Laboratoire d'Immunologie Cellulaire et Tissulaire, 75013 Paris, France c INSERM UMR S 943, Université Pierre et Marie Curie-Paris6, Hôpital Pitié-Salpêtrière, 75013 Paris, France d AP-HP, Groupe hospitalier Pitié-Salpêtrière, Service des Maladies Infectieuses et Tropicales, 75013 Paris, France e Institute for Biomedical Aging Research, Austrian Academy of Sciences, A-6020 Innsbruck, Austria f AP-HP, Groupe hospitalier Pitié-Salpêtrière, Service de Médecine Interne, 75013 Paris, France g AP-HP, Department of Internal Medicine and Infectious Diseases, Bicêtre Hospital, Bicêtre, France h Université Paris-Sud, INSERM U802, Bicêtre, France i HIV/AIDS Division, Department of Internal Medicine, University of California San Francisco, CA, USA.
Abstract
OBJECTIVE AND DESIGN: Increasing evidence support a parallel between HIV-1 infection and immune aging, which is particularly apparent with common changes in naïve versus memory T cell proportions. Here, we aimed at refining the value of common T cell associated markers of immunosenescence during HIV disease progression or aging, and at exploring further the impact in this context of old age as well as CMV co-infection, which is predominant in HIV-1 infected individuals.
METHODS: Frequencies of naïve or CD57 memory T cells as well as the magnitude of CMV-pp65 T cells were measured in HIV-1 infected patients grouped according to disease progression status, treatment and age.
RESULTS: Our results indicate that the decline in naïve T cell levels rather than the accumulation of CD57 senescent T cells identifies best the premature development of an immunosenescence phenotype with HIV disease progression. Moreover, advanced age or mounting of strong CMV specific responses impact independently on CD4 T cell counts and recovery with antiretroviral therapy.
CONCLUSIONS: The present findings indicate that HIV-1 infection amplifies the effect of age on naive T cell levels, and highlight the constraint on the capacity of treated patients to reconstitute their CD4+ T cell compartment due to age and CMV co-infection.
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