CD4 expression on activated NK cells: ligation of CD4 induces cytokine expression and cell migration.
NK cells play an important role in the innate immune response. We have isolated NK cells from human lymphoid tissues and found that these cells express the CD4 molecule on their surface at levels higher than those found on peripheral blood NK cells. To study the functional role of the CD4 molecule on NK cells, we developed an in vitro system by which we are able to obtain robust CD4 expression on NK cells derived from blood. CD4+ NK cells efficiently mediate NK cell cytotoxicity, and CD4 expression does not appear to alter lytic function. CD4+ NK cells are more likely to produce the cytokines gamma-IFN and TNF-alpha than are CD4- NK cells. Ligation of CD4 further increases the number of NK cells producing these cytokines. NK cells expressing CD4 are also capable of migrating toward the CD4-specific chemotactic factor IL-16, providing another function for the CD4 molecule on NK cells. Thus, the CD4 molecule is present and functional on NK cells and plays a role in innate immune responses as a chemotactic receptor and by increasing cytokine production, in addition to its well-described function on T cells as a coreceptor for Ag responsive cell activation.
Bernstein
Helene B
HB
Department of Obstetrics and Gynecology, David Geffen School of Medicine, School of Public Health, University of California, Los Angeles, CA 90095-1740, USA. hbernstein@mednet.ucla.edu
Plasterer
Mary C
MC
Schiff
Sherrie E
SE
Kitchen
Christina M R
CM
Kitchen
Scott
S
Zack
Jerome A
JA
D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007113:Immunity, Innate; D019410:Interleukin-16 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*
D015704:CD4 Antigens; D016207:Cytokines; D019410:Interleukin-16; D008024:Ligands