B- and T-cell responses to the mycobacterium surface antigen PstS-1 in the respiratory tract and adjacent tissues. Role of adjuvants and routes of immunization.
Induction of mucosal immunity in the respiratory tract is crucial for protection against respiratory infections. Here, we have investigated the effects of the routes of immunization as well as of three different adjuvants on the induction of mucosal immune responses. Mice were immunized using intranasal (i.n.) or intraperitoneal (i.p.) routes with the mycobacterium PstS-1 antigen. Cholera toxin (CT), detoxified pertussis toxin (detPT) and RU 41.740 from Klebsiella pneumoniae were compared as mucosal adjuvants. Our data showed that i.n. route of immunization induced the most favorable stimulation of mucosal antigen-specific IgA responses supported by mixed Th cells producing IL-4, IL-5, IFN-gamma. In contrast, i.p. immunizations elicited only enhancement of systemic responses, predominantly of the Th2 type. Furthermore, the use of CT as mucosal adjuvant resulted in the stimulation of a mixed Th cell response whereas detPT evoked mainly Th2 type of responses. Likewise CT, the RU 41.740 adjuvant elicited a mixed Th cell response, albeit supported by much lower numbers of CD4(+) T-cells. Thus, i.n. route of immunization favors the induction of mucosal and systemic immune responses, while the Th cell development at mucosal inductive site is influenced by the adjuvant used for immunizations.
Rodríguez
Ariane
A
Department of Immunology, Stockholm University, Stockholm S-10691, Sweden. ariane@imun.su.se
Troye-Blomberg
Marita
M
Lindroth
Karin
K
Ivanyi
Juraj
J
Singh
Mahavir
M
Fernández
Carmen
C
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000954:Antigens, Surface / Q000008:administration & dosage / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D029968:Escherichia coli Proteins / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000276:immunology*; D033902:Periplasmic Binding Proteins / Q000276:immunology*; D028044:Phosphate-Binding Proteins; D012137:Respiratory System / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D016207:Cytokines; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D033902:Periplasmic Binding Proteins; D028044:Phosphate-Binding Proteins; C090133:PstS protein, E coli