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Currently, our understanding of when and how these cells are generated is limited. We have used an influenza virus mouse infection model to investigate whether the cytokine profile of memory T\u00a0cells is reflective of primary responding cells or skewed toward a distinct profile. We found that, in comparison to primary cells, memory T\u00a0cells tended to make multiple cytokines simultaneously. Analysis of the timings of release of cytokine by influenza virus\u2010specific T\u00a0cells, demonstrated that primary responding CD4 T\u00a0cells from lymphoid organs were unable to produce a sustained cytokine response. In contrast CD8 T\u00a0cells, memory CD4 T\u00a0cells, and primary responding CD4 T\u00a0cells from the lung produced a sustained cytokine response throughout the restimulation period. Moreover, memory CD4 T\u00a0cells were more resistant than primary responding CD4 T\u00a0cells to inhibitors that suppress T\u00a0cell receptor signaling. Together, these data suggest that memory CD4 T\u00a0cells display superior cytokine responses compared to primary responding cells. These data are key to our ability to identify the cues that drive the generation of protective memory CD4 T\u00a0cells following infection.<\/jats:p>","DOI":"10.1002\/eji.201848026","type":"journal-article","created":{"date-parts":[[2019,6,9]],"date-time":"2019-06-09T02:33:59Z","timestamp":1560047639000},"page":"2019-2029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Multifunctional cytokine production reveals functional superiority of memory CD4 T\u00a0cells"],"prefix":"10.1002","volume":"49","author":[{"given":"Lotus M","family":"Westerhof","sequence":"first","affiliation":[{"name":"Centre for Immunobiology Institute of Infection Immunity and Inflammation, 120 University Place University of Glasgow  Glasgow UK"},{"name":"GLAZgo Discovery Centre Institute of Infection Immunity and Inflammation University of Glasgow  Glasgow 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