Aging and it’s Impact on Effector and Memory Cells

Susan L. Swain, Department of Pathology, University of Massachusetts Medical School 

Our studies over the past few years have given us new insights into the diversity of immune mechanisms that memory cells have at their disposal to attack pathogens, that could in other circumstances be directed against transplants. We find that even what appears to be a fairly homogeneous Th1 effector population, gives rise to memory cells that when restimulated carry out a broad array of functions at distinct times and in different locations. Within 2 days, restimulation of memory CD4 T cells leads to an enhanced innate inflammatory response in lung and other sites. Before 5 days the responding cells have helped naïve B cells to ensure a more rapid and effective antibody response via a cognate interaction occurring in peripheral lymphoid organs. During this same timeframe the CD4 memory response enhances the response of CD8 naïve T cells through less well-characterized pathways.  The memory cells in the periphery also expand and differentiate into secondary (2⁰) effectors with kinetics only slightly faster than those of 1⁰ effectors generation. These migrate to the lung by day 6 or so and participate in direct viral clearance via multiple mechanisms including cytotoxicity and IFNg-dependent effects. These multiple activities occurring in different sites can synergize and are able to provide very strong protection against influenza. Because memory cells respond at low antigen dose and require less costimulation than naïve cells, they clearly can present a formidable barrier to transplantation.