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However, CD28-deficient T cells from proteoglycan-immunized animals can proliferate in response to proteoglycan stimulation in vitro , albeit at a rate lower than that in wild-type T cells, which is consistent with the report by Oliveira-dos-Santos et al . [ 30 ] . It has been demonstrated that, in the absence of CD28 engagement, T cells require very high TCR occupancy and prolonged stimulation, whereas CD28 costimulation allows T cells to respond to lower degrees of TCR occupancy [ 30 31 ] . In support of this observation, CD28 -/-mice can still mount immune responses, which vary in magnitude and efficiency depending on the antigen or infectious agent [ 30 32 ] . Our results and those reported by others [ 30 ] suggest that CD28 may regulate the threshold for T-cell activation.