title: Homing potentials of circulating lymphocytes in humans depend on the site of activation: oral, but not parenteral, typhoid vaccination induces circulating antibody-secreting cells that all bear homing receptors directing them to the gut.
abstract: Specific Ab-secreting cells (ASC) appear in the human blood as a response to oral and parenteral vaccination. The actual contribution of these cells to the defense of the body depends on their final effector site. The homing potentials of mucosally and parenterally induced ASC were compared by examining the homing receptor (HR) expression of circulating specific ASC in the blood of volunteers vaccinated orally or parenterally with the same Ag, Salmonella typhi Ty21a. Circulating lymphocytes were separated into receptor-positive and -negative populations, and the numbers of specific ASC were assayed. The alpha4 beta7 integrin, which acts as a gut HR, was expressed on all (99%) of the mucosally activated ASC, but on only 58% of the parenterally induced ASC or 58% of all Ig-secreting cells of the unvaccinated controls. L-selectin, the peripheral lymph node HR, showed an inverse distribution; it was found on 42% of mucosally activated ASC and on 86% of parenterally induced ASC. These results reveal that all of the circulating ASC after oral vaccination are committed to migrate to the mucosal compartment of the immune system, strongly arguing for a recirculation of activated mucosal cells in humans. By contrast, ASC induced by parenteral vaccination with the same Ag are mostly directed to the systemic compartment, yet a part of them has mucosal homing attitudes as well. These differences indicate that the site of Ag encounter determines the homing potential of the cell.
authors.affiliation: National Public Health Institute, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Kantele
authors.forename: J M
authors.initials: JM
authors.lastname: Kantele
authors.forename: E
authors.initials: E
authors.lastname: Savilahti
authors.forename: M
authors.initials: M
authors.lastname: Westerholm
authors.forename: H
authors.initials: H
authors.lastname: Arvilommi
authors.forename: A
authors.initials: A
authors.lastname: Lazarovits
authors.forename: E C
authors.initials: EC
authors.lastname: Butcher
authors.forename: P H
authors.initials: PH
authors.lastname: Mäkelä
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000921:Antibody-Producing Cells / Q000276:immunology*; D018106:CD28 Antigens / Q000096:biosynthesis; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007273:Injections, Intramuscular; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D019041:L-Selectin / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D018106:CD28 Antigens; D006684:HLA-DR Antigens; D007132:Immunoglobulin Isotypes; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D014436:Typhoid-Paratyphoid Vaccines; C071777:integrin alpha4beta7; D019041:L-Selectin