Distinctive lack of CD48 expression in subsets of human dendritic cells tunes NK cell activation.
CD48 is a glycosyl phosphatidylinositol anchor protein known to be virtually expressed by all human leukocytes. Its ligand, 2B4, is a signaling lymphocyte activation molecule-related receptor involved in NK cell activation. Because dendritic cells (DCs) are strong inducers of NK cell functions, we analyzed the expression of CD48 in different human DC subsets. We observed that monocytes differentiating in DCs promptly down-regulate CD48. Similarly, DCs isolated from inflamed lymph nodes generally do not express CD48. Plasmocytoid DCs do not express CD48 either, whereas myeloid DCs harbored in blood, bone marrow, and thymus express it. In addition, we showed that CD48 expression in DCs affects NK cell functions during NK/DC cross-talk, because NK cells obtained from normal donors and from X-linked lymphoproliferative disease patients are, respectively, triggered or inhibited by DCs expressing surface CD48. Remarkably, IFN-gamma production by lymph node NK cells, in contrast to blood NK cells, can be negatively modulated by 2B4/CD48 interactions, indicating a 2B4 inhibitory pathway in lymph node NK cells. Therefore, the CD48 deficiency of DCs harbored in inflamed lymph nodes that we report in this study might be relevant to successfully activate lymph node NK cells in the early phase of the immune response. Our results show that distinct subsets of human DCs, differently from all other mononuclear hemopoietic cells, specifically do not express CD48. Moreover, the expression of CD48 depends on the anatomic location of DCs and might be related to the tissue-specific 2B4 function (activating or inhibitory) of the NK cells with which they interact.
Morandi
Barbara
B
Istituto Nazionale Ricerca sul Cancro, Genoa, Italy.
Costa
Roberta
R
Falco
Michela
M
Parolini
Silvia
S
De Maria
Andrea
A
Ratto
Giovanni
G
Mingari
Maria Cristina
MC
Melioli
Giovanni
G
Moretta
Alessandro
A
Ferlazzo
Guido
G
D015703:Antigens, CD / Q000032:analysis* / Q000378:metabolism; D000071178:CD48 Antigen; D003713:Dendritic Cells / Q000737:chemistry* / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology*; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D007371:Interferon-gamma