title: The state of CD4+ T cell activation is a major factor for determining the kinetics and location of T cell responses to oral antigen.
abstract: Current models suggest that inductive immune responses to enteric Ag are initiated in Peyer's patches (PP) and mesenteric lymph nodes (MLN) followed by migration of activated, memory-like CD4(+) T cells to extralymphoid sites in the intestinal lamina propria (LP). The resultant immune system contains both naive and activated T cells. To examine the differential responses of naive and memory-like T cells to oral Ag, bone marrow chimeras (BMC) were generated. Irradiated BALB/c hosts were reconstituted with a mix of DO11.10 x RAG-1(-/-) and BALB/c bone marrow. In unprimed DO11.10 and BMC models, LP and PP DO11.10 T cells responded to oral Ag with similar kinetics. Responses of activated, memory-like T cells to oral Ag were examined in thymectomized BMC 60 days after i.p. immunization with OVA peptide in Freund's adjuvant (OVA(323-339)/CFA). Results indicate that i.p. OVA(323-339)/CFA generated a high proportion of memory-like CD45RB(low) DO11.10 T cells in peripheral lymphoid (40%) and intestinal LP (70%) tissue. Previously activated DO11.10 T cells in the LP responded to oral Ag earlier and at 50% higher levels compared with memory CD4(+) T cells localized to PP tissue. These data indicate that responses to oral Ag in antigenically naive animals are initiated in PP whereas in Ag-experienced animals LP T cells respond earlier and more vigorously than cells in PP. Taken together, these data suggest that previous activation alters the hierarchy of T cell responses to oral Ag by enhancing the efficiency of LP T cell activation.
authors.affiliation: Department of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Hae-ock
authors.initials: HO
authors.lastname: Lee
authors.forename: Cristine J
authors.initials: CJ
authors.lastname: Cooper
authors.forename: Jung-hee
authors.initials: JH
authors.lastname: Choi
authors.forename: Ziad
authors.initials: Z
authors.lastname: Alnadjim
authors.forename: Terrence A
authors.initials: TA
authors.lastname: Barrett
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D007399:Interphase / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology*; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011828:Radiation Chimera / Q000276:immunology
chemical_list: D000941:Antigens; C111390:OVA 323-339; D010446:Peptide Fragments; D010047:Ovalbumin