CD4+/CD8+ macrophages infiltrating at inflammatory sites: a population of monocytes/macrophages with a cytotoxic phenotype.
We found a population of nonlymphoid cells expressing both CD4 and CD8 in peripheral blood mononuclear cells (PBMCs) of human T-cell leukemia virus type-I pX transgenic rats with autoimmune diseases. These cells, which showed a monocytic phenotype, were also found in wild-type rats, and their number increased by adjuvant-assisted immunization. GM-CSF increased the number of these double-positive (DP) monocytes in PBMCs. Consistent with the idea that DP monocytes differentiate into DP macrophages at sites of inflammation, we found infiltration of DP macrophages at the site of myosin-induced myocarditis in wild-type rats; these cells exhibited a T-helper 1 (Th1)-type cytokine/chemokine profile and expressed high levels of Fas ligand, perforin, granzyme B, and NKR-P2 (rat orthologue of human NKG2D). Adoptive transfer of GFP-positive spleen cells confirmed hematogenous origin of DP macrophages. DP monocytes had a cytotoxic phenotype similar to DP macrophages, indicating that this phenotypic specialization occurred before entry into a tissue. In line with this, DP monocytes killed tumor cells in vitro. Combined evidence indicates that certain inflammatory stimuli that induce GM-CSF trigger the expansion of a population of DP monocytes with a cytotoxic phenotype and that these cells differentiate into macrophages at inflammatory sites. Interestingly, human PBMCs also contain DP monocytes.
Baba
Tomohisa
T
Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
Ishizu
Akihiro
A
Iwasaki
Sari
S
Suzuki
Akira
A
Tomaru
Utano
U
Ikeda
Hitoshi
H
Yoshiki
Takashi
T
Kasahara
Masanori
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D030801:Animals, Genetically Modified; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D053804:Granzymes; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009369:Neoplasms / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D051381:Rats; D011971:Receptors, Immunologic / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D019076:Transgenes / Q000276:immunology
D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C113208:NKR-P2 protein, rat; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases