Induction and visualization of mucosal memory CD8 T cells following systemic virus infection.
Whether CD8 T cell memory exists outside secondary lymphoid organs is unclear. Using an adoptive transfer system that enables tracking of OVA-specific CD8 T cells, we explored the antigenic requirements for inducing CD8 T cell memory and identified intestinal mucosa memory cells. Although systemic immunization with soluble OVA induced clonal expansion, memory CD8 cells were not produced. In contrast, infection with virus-encoding OVA induced memory CD8 cells in the periphery and the lamina propria and intraepithelial compartments of the intestinal mucosa. Mucosal memory cells expressed a distinct array of adhesion molecules as compared with secondary lymphoid memory cells, suggesting that there may be separate mucosal and systemic memory pools. Mucosal CD8 memory cells rapidly produced IFN-gamma after Ag stimulation. Reactivation of memory cells by Ag feeding resulted in increased cell size and up-regulation of CD28 and CD11c. CD8 mucosal memory cells exhibited ex vivo lytic activity that was up-regulated dramatically following Ag reencounter in vivo. Interestingly, reactivation of memory cells did not require CD28-mediated costimulation. The ability of the intestinal mucosa to maintain CD8 memory cells provides a potential mechanism for effective mucosal vaccination.
Kim
S K
SK
Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington 06030, USA.
Schluns
K S
KS
Lefrançois
L
L
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D018353:Rhabdoviridae Infections / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D000956:Antigens, Viral; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D010047:Ovalbumin