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A model for mapping the fate of CD8+ T cells that have expressed granzyme B (GzmB)
Author(s) -
Bannard Oliver Michael,
Fearon Douglas
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.846.19
Subject(s) - biology , cytotoxic t cell , cd8 , microbiology and biotechnology , granzyme b , effector , lymphocytic choriomeningitis , ctl* , immunology , cancer research , in vitro , immune system , genetics
Commitment to effector differentiation of the CD8+ T cell may be associated with senescence. To define when this occurs, it is necessary to indelibly mark a cell during development and follow its fate without artificial interventions. We have generated a BAC transgenic mouse line that expresses a tamoxifen‐regulated Cre/ERT2 recombinase controlled by transcriptional elements of the effector gene, Gzmb . Crossing these mice with the R26R‐EYFP Cre reporter line permits conditional, permanent expression of EYFP in cells that had transcribed Gzmb . Stimulation in vitro under GzmB‐inducing conditions caused expression of EYFP in up to 50% of GzmB+ CD8+ T cells from these mice, only in GzmB+ cells, and only with tamoxifen. Influenza infection caused tamoxifen‐dependent EYFP expression by 21% and 31% of nucleoprotein (NP)‐specific CD8+ T cells in the spleen and lung, all of which were GzmB+. Six weeks post‐infection the splenic number decreased to 15%, all EYFP+ cells were now GzmB−, and were CD62L high or low. After secondary infection without tamoxifen, the number of EYFP+ CD8+ T cells in the lung increased ∼100‐fold, indicating a capacity for clonal expansion despite prior expression of GzmB. Thus, we now have a model with which we can map the fate of CD8+ T cells that have transcribed Gzmb at a specified time during repetitive or persistent viral infections, irrespective of continued expression of the gene. Wellcome Trust.