title: Functional deficits of pertussis-specific CD4+ T cells in infants compared to adults following DTaP vaccination.
abstract: Understanding the immune responses that explain why infants require multiple doses of pertussis vaccine to achieve protection against infection is a high priority. The objective of this study was to compare the function and phenotypes of antigen-specific CD4(+) T cells in adults (n=12), compared to infants (n=20), following vaccination with acellular pertussis (DTaP) vaccine. Peripheral blood mononuclear cells (PBMCs) were stimulated with pertussis toxoid (PT), pertactin (PRN) and filamentous haemagglutinin (FHA). Multi-parameter flow cytometry was used to delineate CD4(+) T cell populations and phenotypes producing interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α and IL-4. Based on surface CD69 expression, infants demonstrated activation of vaccine antigen-specific CD4(+) T cells similar to adults. However, among infants, Boolean combinations of gates suggested that type 1 (Th-1) CD4(+) T cell responses were confined largely to TNF-α(+) IL-2(+) IFN-γ(-) or TNF-α(+) IL-2(-) IFN-γ(-) . A significantly lower percentage of polyfunctional T helper type 1 (Th1) responses (TNF-α(+) IFN-γ(+) IL-2(+) ) and type 2 (Th2) responses (IL-4) were present in the infants compared to adults. Moreover, a significantly higher percentage of infants' functional CD4(+) T cells were restricted to CD45RA(-) CCR7(+) CD27(+) phenotype, consistent with early-stage differentiated pertussis-specific memory CD4(+) T cells. We show for the first time that DTaP vaccination-induced CD4(+) T cells in infants are functionally and phenotypically dissimilar from those of adults.
authors.affiliation: Center for Infectious Diseases and Immunology, Research Institute, Rochester General Hospital, Rochester, NY 14621, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Sharma
authors.forename: M E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001886:Bordetella pertussis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D037181:Lectins, C-Type / Q000032:analysis; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D000099192:CD69 Antigens
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D004768:Enterotoxins; D037181:Lectins, C-Type; D008222:Lymphokines; D000099192:CD69 Antigens; C031818:enterotoxin B, staphylococcal