University of Arkansas, Fayetteville


Immunological memory, acquired either by previous infection or vaccination, affords vertebrates a large margin of survival. Subsequent exposure to a "remembered" pathogen signals memory cells to undergo a rapid, clonal proliferation into armed effector cells. This rapidly mobilized clone mediates the specific clearance of the trespassing pathogen. Typically, this secondary recall response effectively dispatches the particular pathogen prior to any manifest disease pathology. This is the age-old, enjoyed benefit of immunity. Though this appreciation for immunological memory has been in documentation for nearly 3 millennia, our ability to intentionally increase its normal level of formation is only now beginning. The Durdik lab and collaborators previously demonstrated that the presence of pentoxifylline (PF), a clinically administered phosphodiesterase inhibitor, during priming, produces a decrease in the primary response and a substantially increased memory response within the CD4 helper T-cell contingent. Here it is shown that the presence of PF during priming results in enhanced CD8 cytotoxic secondary responses. CD8 T-cells respond by directly killing cells hosting intracellular infections. A significantly enhanced cytotoxic memory response was demonstrated both 60 and 90 days post-priming to a specific peptide antigen called HY (amino acid sequence: KCSRNRQYL) under a PF-cover during priming, in contrast to groups without PF administration. These findings suggest a substantial potential for the development of enhanced vaccines for intracellular pathogens.