gammadelta T cells of human early pregnancy decidua: evidence for cytotoxic potency.
The immune compromise in decidua allows a semiallogeneic fetus to survive without impairing the ability of the maternal immune system to fight infections. Cytotoxic mechanisms are likely to be important in this compromise. Using RT-PCR, immunoflow cytometry and immunoelectron microscopy, the cytotoxic potential of isolated human decidual gammadelta T cells was studied. mRNA for perforin (Pf), granzymes A and B, granulysin and Fas ligand (FasL) was simultaneously expressed in decidual gammadelta T cells. Pf and FasL were not expressed on the cell surface. However, the cells constitutively synthesized Pf and stored it in cytolytic granules. Within the granules Pf mainly resided in the granule core formed by Pf-containing microvesicles. Ultrastructurally, three groups of Pf-containing granules were distinguished. They probably represent different stages of granule maturation in a process where Pf-containing microvesicles first attach to the core cortex and then are translocated across the cortex into the core. Presynthesized FasL was also stored in the core and microvesicles of the cytolytic granules. Upon degranulation by ionomycin/Ca(2+) treatment, FasL was rapidly translocated to the cell surface, demonstrating that its surface expression was not controlled by de novo biosynthesis. Thus decidual gammadelta T cells appear to perform Pf- and FasL-mediated cytotoxicity utilizing a common secretory mechanism based on cytolytic granule exocytosis. The first cytochemical visualization of lipids in the cytolytic granules is provided. These intragranular lipids probably wrap up the core and participate in packaging of the cytotoxic proteins as well as in the killing process. An ultrastructural model of a cytolytic granule is presented.
Mincheva-Nilsson
L
L
Departments of Clinical Immunology and. Immunology, Umeå University, 90185 Umeå, Sweden.
Nagaeva
O
O
Sundqvist
K G
KG
Hammarström
M L
ML
Hammarström
S
S
Baranov
V
V
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D003656:Decidua / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes; D006801:Humans; D008055:Lipids / Q000032:analysis; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D054353:Perforin; D010618:Phenanthrolines / Q000494:pharmacology; D052899:Pore Forming Cytotoxic Proteins; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure
D000945:Antigens, Differentiation, T-Lymphocyte; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C075005:GNLY protein, human; D008055:Lipids; D008562:Membrane Glycoproteins; D010618:Phenanthrolines; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; C025205:1,10-phenanthroline