Expression of CD4 on human peripheral blood neutrophils.
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 gammadelta 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-1-infected 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.
Biswas
Priscilla
P
Laboratory of Clinical Immunology, San Raffaele Scientific Institute, Milan, Italy. priscilla.biswas@hsr.it
Mantelli
Barbara
B
Sica
Antonio
A
Malnati
Mauro
M
Panzeri
Carla
C
Saccani
Alessandra
A
Hasson
Hamid
H
Vecchi
Andrea
A
Saniabadi
Abby
A
Lusso
Paolo
P
Lazzarin
Adriano
A
Beretta
Alberto
A
D001773:Blood Cells; D015704:CD4 Antigens / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger