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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-10-3056.
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Blood, 1 June 2003, Vol. 101, No. 11, pp. 4452-4456
IMMUNOBIOLOGY
Expression of CD4 on human peripheral blood neutrophils
Priscilla Biswas,
Barbara Mantelli,
Antonio Sica,
Mauro Malnati,
Carla Panzeri,
Alessandra Saccani,
Hamid Hasson,
Andrea Vecchi,
Abby Saniabadi,
Paolo Lusso,
Adriano Lazzarin, and
Alberto Beretta
From the Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy; Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Unit of Human Virology, San Raffaele Scientific Institute, Milan, Italy; Microscopy Service, San Raffaele Scientific Institute, Milan, Italy; Mario Negri Institute for Pharmacologic Research, Milan, Italy; and Japan Immunoresearch Laboratories, Takasaki, Japan.
CD4, the primary receptor for entry of HIV, is known to be expressed on T cells and monocytes/macrophages; healthy natural killer (NK) lymphocytes; in vitro human herpesvirus 6 (HHV6)infected CD8+, NK, and  T lymphocytes; CD34+ progenitor cells; and a subset of eosinophils and basophils. We here report the unconventional expression of CD4 at the surface of peripheral blood neutrophils derived from 4 of 51 (7.8%) HIV-1infected and 3 of 25 (12%) uninfected donors, with similar frequency within the 2 groups. The percentage of CD4+ neutrophils ranged from 39% to 97% of the total neutrophil population. Both surface and cytoplasmic forms of CD4 were present in neutrophils. Quantitative RNA polymerase chain reaction (PCR) revealed that neutrophils contain levels of CD4 mRNA comparable to those of peripheral blood mononuclear cells derived from the same donor. The conformation of CD4 expressed at the surface of neutrophils was similar to that of CD4 expressed on T lymphocytes as determined by the binding of monoclonal antibodies specific for conformational epitopes and the binding of recombinant HIV-1 gp120. Thus, our data provide evidence that neutrophils express endogenous CD4 and bind HIV. Owing to their abundance in peripheral blood, CD4+ neutrophils may influence significantly the biodistribution of HIV delivering it to sites of inflammation or to additional tissue reservoirs.

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