Non-equilibrium and differential function between intraepithelial and lamina propria virus-specific TCRalphabeta(+) CD8alphabeta(+) T cells in the small intestinal mucosa.
The gastrointestinal mucosa regularly encounters commensal and pathogenic microbiota. Gut mucosal lymphocytes consist of two phenotypically different populations residing in the intestinal intraepithelial (IEL) compartment and lamina propria (LP). Little is known about compositional and functional differences of antigen-specific T cells from these mucosal compartments after mucosal infection, or the degree of trafficking between them. We here studied the B8R(20-27)-specific CD8 T-cell response in LP and IEL compartments after intrarectal immunization with modified vaccinia virus Ankara (MVA). CD8(+) T cells in the IEL compartment had much lower avidity than in the LP or spleen during acute and memory phases. Surprisingly, the TCR Vbeta-chain distribution of antigen-specific T cells and the length of the CDR3 region of the dominant Vbeta genes showed substantial dissimilarities between IEL and LP antigen-specific CD8alphabeta T cells in individual mice, increasing with time. We show functional and compositional differences between these mucosal compartments during the effector and memory phases of the immune response, indicating limited crosstalk and microenvironmental differences between the IEL, LP, and spleen. The restricted migration of cells from each of these mucosal compartments could partly account for a founder effect we observed in the IEL TCRalphabeta CD8alphabeta epitope-specific repertoire that might impact protective efficacy.
Isakov
D
D
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Dzutsev
A
A
Belyakov
I M
IM
Berzofsky
J A
JA
D000285:Administration, Rectal; D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D002465:Cell Movement; D004848:Epithelium / Q000276:immunology; D005260:Female; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014616:Vaccinia virus / Q000276:immunology*
D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma