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.
Huleatt
J W
JW
Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA. James.Huleatt@Yale.edu
Pilip
I
I
Kerksiek
K
K
Pamer
E G
EG
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