A role for IFN-gamma from antigen-specific CD8+ T cells in protective immunity to Listeria monocytogenes.
Whether IFN-gamma contributes to the per-cell protective capacity of memory CD8(+) T cells against Listeria monocytogenes (LM) has not been formally tested. In this study, we generated LM Ag-specific memory CD8(+) T cells via immunization of wild-type (WT) and IFN-gamma-deficient (gamma knockout (GKO)) mice with LM peptide-coated dendritic cells and compared them phenotypically and functionally. Immunization of WT and GKO mice resulted in memory CD8(+) T cells that were similar in number, functional avidity, TCR repertoire use, and memory phenotype. The protective capacity of memory CD8(+) T cells from immunized WT and GKO mice was evaluated after adoptive transfer of equal numbers of WT or GKO cells into naive BALB/c mice followed by LM challenge. The adoptively transferred CD8(+) T cells from GKO donors exhibited a decreased ability to reduce bacterial numbers in the organs of recipient mice when compared with an equivalent number of Ag-matched WT CD8(+) T cells. This deficiency was most evident early (day 3) after infection if a relatively low infectious dose was used; however, transferring fewer memory CD8(+) T cells or increasing the LM challenge dose revealed a more pronounced defect in protective immunity mediated by the CD8(+) T cells from GKO mice. Our studies identified a decrease in Ag-specific target cell lysis in vivo by CD8(+) T cells from GKO mice as the mechanism for the decreased protective immunity after LM challenge. Further studies suggest that the lack of IFN-gamma production by the Ag-specific CD8 T cells themselves diminishes target cell sensitivity to cytolysis, thereby reducing the lytic potency of IFN-gamma-deficient LM-specific memory CD8(+) T cells.
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Kelly A N
KA
Messingham
Vladimir P
VP
Badovinac
Ali
A
Jabbari
John T
JT
Harty
D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005260:Female; D007114:Immunization; D007156:Immunologic Memory / Q000235:genetics; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013997:Time Factors
D000942:Antigens, Bacterial; D007371:Interferon-gamma