The restricted expression of granzyme M in human lymphocytes.
We have analyzed the expression of human granzyme M (Gzm M) in various human leukocyte subsets using the specific mAb 4H10. Using FACS and Western blotting analysis we compared the expression of Gzm M with that of other granzymes (Gzm A and Gzm B) and the lytic protein perforin. Human Gzm M was constitutively highly expressed in NK cells as was perforin and Gzm A. Surprisingly, freshly isolated NK cells had very low (sometimes undetectable) levels of Gzm B. In contrast to Gzm B and perforin, Gzm M was not detected in highly purified CD4(+) and CD8(+) T cells either constitutively or after short term activation in vitro. However, low levels of Gzm M were observed in some T cell clones on prolonged passage in vitro. Gzm M was not detected in highly purified neutrophils, monocytes, or tumor cells of the myelomonocytic lineage. Examination of minor T cell subsets from human peripheral blood showed detectable Gzm M in CD3(+), CD56(+) T cells and gammadelta T cells. A histological staining procedure was developed that demonstrated a granular staining pattern for Gzm M and a cellular distribution similar to that observed by Western blotting. These data indicate that the expression of Gzm M does not always correlate with the lytic activity of cytotoxic cells. However, expression of Gzm M in NK cells, CD3(+), CD56(+) T cells, and gammadelta T cells suggests that this enzyme may play some role in innate immune responses.
Sayers
T J
TJ
Intramural Research Support Program, Science Applications International Corporation-Frederick, Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702-1201, USA. sayers@mail.ncifcrf.gov
Brooks
A D
AD
Ward
J M
JM
Hoshino
T
T
Bere
W E
WE
Wiegand
G W
GW
Kelly
J M
JM
Smyth
M J
MJ
Kelley
J M
JM
D015153:Blotting, Western; D017252:CD3 Complex / Q000096:biosynthesis; D019002:CD56 Antigen / Q000096:biosynthesis; D002460:Cell Line; D002469:Cell Separation; D002999:Clone Cells; D005434:Flow Cytometry; D053804:Granzymes; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000201:enzymology; D016131:Lymphocyte Subsets / Q000201:enzymology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000276:immunology / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000201:enzymology; D020298:U937 Cells
D017252:CD3 Complex; D019002:CD56 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054353:Perforin; C509213:GZMB protein, human; C509218:GZMM protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human