Cutting edge: rapid and efficient in vivo cytotoxicity by cytotoxic T cells is independent of granzymes A and B.
Cytotoxic T (Tc) cells lyse target cells via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and in the absence of gzm A and B the induction of apoptosis is severely impaired. However, using in vivo Tc cell killing assays, we find that virus-immune, gzm A x B-deficient (gzmAxB(-/-)) mice are competent to eliminate adoptively transferred target cells pulsed with an immunodominant Tc cell determinant as rapidly and completely as their wild-type counterparts. Specific target cell elimination occurred with similar kinetics in both spleen and lymph nodes. Thus, neither gzmA nor gzmB are required for rapid and efficient in vivo cytotoxicity by Tc cells.
Regner
Matthias
M
John Curtin School of Medical Research, Canberra, Australia. Matthias.Regner@anu.edu.au
Pavlinovic
Lisa
L
Koskinen
Aulikki
A
Young
Nicolie
N
Trapani
Joseph A
JA
Müllbacher
Arno
A
D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004481:Ectromelia virus / Q000276:immunology; D004482:Ectromelia, Infectious / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D053804:Granzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013997:Time Factors
D053804:Granzymes; C509214:Gzmb protein, mouse