IL-13 driven Th2 immunity is indispensable for host protection against
infection with the gastrointestinal nematode Nippostronglus brasiliensis. Disruption of CD28 mediated costimulation impairs development of adequate Th2 immunity, showing an importance for CD28 during the initiation of an immune response against this pathogen. In this study, we used global CD28⁻/⁻ mice and a recently established mouse model that allows for inducible deletion of the cd28 gene by
oral administration of
tamoxifen (CD28(-/lox)Cre⁺/⁻+TM) to resolve the controversy surrounding the requirement of CD28 costimulation for recall of protective memory responses against pathogenic
infections. Following primary
infection with N. brasiliensis, CD28⁻/⁻ mice had delayed expulsion of adult worms in the small intestine compared to wild-type C57BL/6 mice that cleared the
infection by day 9 post-
infection. Delayed expulsion was associated with reduced production of
IL-13 and reduced serum levels of
antigen specific
IgG1 and total
IgE. Interestingly, abrogation of CD28 costimulation in CD28(-/lox)Cre⁺/⁻ mice by
oral administration of
tamoxifen prior to
secondary infection with N. brasiliensis resulted in impaired worm expulsion, similarly to infected CD28⁻/⁻ mice. This was associated with reduced production of the Th2
cytokines IL-13 and
IL-4, diminished serum titres of
antigen specific
IgG1 and total
IgE and a reduced CXCR5⁺ T(FH) cell population. Furthermore, total number of CD4⁺ T cells and B220⁺ B cells secreting Th1 and Th2
cytokines were significantly reduced in CD28⁻/⁻ mice and
tamoxifen treated CD28(-/lox)Cre⁺/⁻ mice compared to C57BL/6 mice. Importantly, interfering with CD28 costimulatory signalling before
re-infection impaired the recruitment and/or expansion of central and effector memory CD4⁺ T cells and follicular B cells to the draining lymph node of
tamoxifen treated CD28(-/lox)Cre⁺/⁻ mice. Therefore, it can be concluded that CD28 costimulation is essential for conferring host protection during secondary N. brasiliensis
infection.