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Low CD4+ T-Cell Surface CCR5 Density as a Cause of Resistance to In Vivo HIV-1 Infection

Reynes, Jacques; Baillat, Vincent; Portales, Pierre; Clot, Jacques; Corbeau, Pierre

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 September 2003 - Volume 34 - Issue 1 - pp 114-116
Letters to the Editor

From the Service des Maladies Infectieuses

et Tropicales, Hôpital Gui de Chauliac

(Drs Reynes and Baillat)

Laboratoire d'Immunologie, Hôpital

Saint Eloi (Drs Portales, Clot, and Corbeau)

Institut de Génétique Humaine CNRS

UPR114Z Montpellier, France (Dr Corbeau)

To the Editor:

We have recently shown that the mean number of CCR5 coreceptors at the surface of CD4+ cells strongly determines the efficiency of HIV-1 life cycle in vitro. 1 For this reason, we have tested the hypothesis that low CD4+ T-cell surface CCR5 density could favor resistance to HIV-1 infection in vivo. For this purpose, using a quantitative flow cytometry assay, 2 we measured CCR5 expression in 24 HIV-1-seronegative adults (14 men and 10 women) with multiple high-risk sexual exposures to HIV-1. Figure 1 shows that exposed uninfected subjects expressed low CCR5 densities (arithmetics means of 9273 [95% CI, 7661–10,885] CCR5 molecules per cell) compared with 84 sex-matched nonexposed control HIV-negative individuals (arithmetics means of 11,145 [95% CI, 10,379–11,911]P = 0.05).

As we have previously shown that CD4+ T-cell surface CCR5 density is stable over time for a given individual, 2 these results argue for the fact that low CCR5 expression could participate, in addition to virologic factors, to immune responses or to antiviral factors produced by CD8+ T cells in the resistance to HIV-1 infection. 3 They also explain why subjects heterozygous for the CCR5 32 base-pair deletion (Δ32) allele, who express low CCR5 densities, 4 might be more resistant to HIV-1 infection. 5,6 Moreover, our data are consistent with previous works reporting, in conflict with others, 7 that CD4+ T cells from some exposed uninfected subjects are less susceptible to HIV-1 infection 8,9 and that these CD4+ T cells show low surface expression of CCR5. 8,10

Our data further emphasize the key role played in HIV-1 infection by CD4+ T-cell surface CCR5 density, which influences in vivo infectibility (this work), virus load, 2 disease progression, 11 and response to treatment. 12

Jacques Reynes

Vincent Baillat

Pierre Portales

Jacques Clot

Pierre Corbeau

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