Granzyme K expressing cytotoxic T lymphocytes protects against influenza virus in granzyme AB-/- mice.
Granzyme (grz) AB(-/-) H2(b) mice generate numerically normal cytotoxic T lymphocyte (CTL) responses to the prominent influenza A virus D(b) NP(366) and D(b) PA(224) epitopes and terminate the infectious process in the pneumonic lung with the same kinetics as the WT controls. Though grz B protein expression is fully compromised, there is only a partial effect on the level of CTL activity measured in a classical, short-term (51)Cr release assay. Single-cell polymerase chain reaction (PCR) analysis of both highly activated effector and "resting" memory CD8(+) T cells from influenza A virus-infected grzAB(-/-) mice showed a high prevalence of grzK mRNA(+) expression in tetramer (tet)(+) CTLs as was found in WT mice. However, a marked reduction in cytotoxicity present in the primary splenic CTLs of grzAB(-/-) mice correlated with decreased grzK expression, as measured by real-time PCR. This suggests that grzK plays an important role in CD8(+) T-cell cytotoxicity both in the presence and absence of grzA and B.
Jenkins
Misty R
MR
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia. mrj33@cam.ac.uk
Trapani
Joseph A
JA
Doherty
Peter C
PC
Turner
Stephen J
SJ
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D053804:Granzymes / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology*
D053804:Granzymes