Intestinal and splenic T cell responses to enteric Listeria monocytogenes infection: distinct repertoires of responding CD8 T lymphocytes.
Listeria monocytogenes is an intracellular bacterium that causes systemic infections after traversing the intestinal mucosa. Clearance of infection and long term protective immunity are mediated by L. monocytogenes-specific CD8 T lymphocytes. In this report, we characterize the murine CD8 T cell response in the lamina propria and intestinal epithelium after enteric L. monocytogenes infection. We find that the frequency of MHC class Ia-restricted, L. monocytogenes-specific T cells is approximately 4- to 5-fold greater in the lamina propria than in the spleen of mice after oral or i.v. infection. Although the kinetics of T cell expansion and contraction are similar in spleen, lamina propria, and intestinal epithelium, high frequencies of Ag-specific T cells are detected only in the lamina propria 1 mo after infection. In contrast to MHC class Ia-restricted T cells, the frequency of H2-M3-restricted, L. monocytogenes-specific T cells is decreased in the intestinal mucosa relative to that found in the spleen. In addition to this disparity, we find that MHC class Ia-restricted CD8 T cells specific for a dominant L. monocytogenes epitope have different TCR V beta repertoires in the spleen and intestinal mucosa of individual mice. These findings indicate that the intestinal mucosa is a depot where L. monocytogenes-specific effector CD8 T cells accumulate during and after infection irrespective of immunization route. Furthermore, our results demonstrate that CD8 T cell populations in these two sites, although overlapping in Ag specificity, are distinct in terms of their repertoire.
Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA. James.Huleatt@Yale.edu
J W
JW
Huleatt
I
I
Pilip
K
K
Kerksiek
E G
EG
Pamer
D000818:Animals; D001427:Bacterial Toxins; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004751:Enteritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007114:Immunization; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007441:Intubation, Gastrointestinal; D007700:Kinetics; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C038705:hlyA protein, Listeria monocytogenes