Functional deficits of pertussis-specific CD4+ T cells in infants compared to adults following DTaP vaccination.

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.