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J. Virol. doi:10.1128/JVI.01401-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Preserved central memory and activated effector memory CD4+ T cell subsets in HIV controllers: an ANRS EP36 study

Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris; Institut National de la Santé et de la Recherche Médicale U 802, Université Paris XI, Centre Hospitalo-Universitaire Bicêtre, Bicêtre; Service de Médecine Interne et Maladies Infectieuses, AP-HP, CHU Bicêtre, Bicêtre; Unité des Régulations des Infections Rétrovirales, Institut Pasteur, Paris; Institut National de la Santé et de la Recherche Médicale U 822, Centre Hospitalo-Universitaire Bicêtre, Bicêtre

^* To whom correspondence should be addressed. Email: chakra{at}pasteur.fr.

	Abstract

HIV controllers are rare individuals who spontaneously control HIV-1 replication for 10 years or more in the absence of antiretroviral treatment. HIV controllers (n=11) maintained potent HIV-specific CD4 responses in spite of very low antigenic load. Their central memory (CM) CD4+ T cells were characterized by near normal numbers, preserved IL-2 secretion in response to HIV antigens, and uniformly high expression of the survival receptor IL-7R. Controllers expressed CCR7 at higher levels than uninfected controls, suggesting differences in T_CM cell homing patterns. Effector memory (EM) CD4+ T cell responses were polyfunctional in HIV controllers, while IL-2 secretion was lost in viremic patients. Cytokine production was 3 times higher in controllers than in HAART-treated patients with undetectable viral load, suggesting an intrinsically more efficient response in the former group. The total CD4+ T_EM cell pool underwent immune activation in controllers, as indicated by increased HLA-DR expression, decreased IL-7R expression, a bias toward IFN- production upon polyclonal stimulation, and increased MIP-1 secretion associated with chronic CCR5 down-regulation. Thus, HIV controllers showed a preserved CD4+ T_CM cell compartment and signs of a potent functional activation in the CD4+ T_EM cell compartment. While controllers did not show the generalized immune activation pattern associated with disease progression, they had signs of immune activation restricted to the effector compartment. These findings suggest the induction of an efficient, non-detrimental type of immune activation in patients who spontaneously control HIV.