We have analyzed the expression of human granzyme M (Gzm M) in various huma
n leukocyte subsets using the specific mAb 4H10, Using FAGS and Western blo
tting analysis we compared the expression of Gzm M with that of other granz
ymes (Gzm A and Gzm B) and the lytic protein perforin, Human Gzm M was cons
titutively highly expressed in NK cells as was perforin and Gzm A. Surprisi
ngly, freshly isolated NK cells had very low (sometimes undetectable) level
s of Gzm B. In contrast to Gzm B and perforin, Gzm M was not detected in hi
ghly purified CD4(+) and CD8(+) T cells either constitutively or after shor
t term activation in vitro. However, low levels of Gzm M were observed in s
ome T cell clones on prolonged passage in vitro. Gzm M was not detected in
highly purified neutrophils, monocytes, or tumor cells of the myelomonocyti
c lineage. Examination of minor T cell subsets from human peripheral blood
showed detectable Gzm M in CD3(+), CD56(+) T cells and gamma delta T cells.
A histological staining procedure was developed that demonstrated a granul
ar staining pattern for Gzm M and a cellular distribution similar to that o
bserved by Western blotting. These data indicate that the expression of Gzm
M does not always correlate with the lytic activity of cytotoxic cells. Ho
wever, expression of Gzm M in NK cells, CD3(+), CD56(+) T cells, and gamma
delta T cells suggests that this enzyme may play some role in innate immune
responses.