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The choreography of complex immune responses, including the priming, differentiation, and modulation of specific effector T cell populations generated in the immediate wake of an acute pathogen challenge, is in part controlled by chemokines, a large family of mostly secreted molecules involved in chemotaxis and other patho/physiological processes. T cells are both responsive to various chemokine cues and a relevant source for certain chemokines themselves; yet, the actual range, regulation, and role of effector T cell-derived chemokines remains incompletely understood. In this study, using different in vivo mouse models of viral and bacterial infection as well as protective vaccination, we have defined the entire spectrum of chemokines produced by pathogen-specific CD8 + and CD4 + T effector cells and delineated several unique properties pertaining to the temporospatial organization of chemokine expression patterns, synthesis and secretion kinetics, and cooperative regulation. Collectively, our results position the "T cell chemokine response" as a notably prominent, largely invariant, yet distinctive force at the forefront of pathogen-specific effector T cell activities and establish novel practical and conceptual approaches that may serve as a foundation for future investigations into the role of T cell-produced chemokines in infectious and other diseases., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Pathogen-specific memory T cells (T M ) contribute to enhanced immune protection under conditions of reinfection, and their effective recruitment into a recall response relies, in part, on cues imparted by chemokines that coordinate their spatiotemporal positioning. An integrated perspective, however, needs to consider T M as a potentially relevant chemokine source themselves. In this study, we employed a comprehensive transcriptional/translational profiling strategy to delineate the identities, expression patterns, and dynamic regulation of chemokines produced by murine pathogen-specific T M CD8 + T M , and to a lesser extent CD4 + T M , are a prodigious source for six select chemokines (CCL1/3/4/5, CCL9/10, and XCL1) that collectively constitute a prominent and largely invariant signature across acute and chronic infections. Notably, constitutive CCL5 expression by CD8 + T M serves as a unique functional imprint of prior antigenic experience; induced CCL1 production identifies highly polyfunctional CD8 + and CD4 + T M subsets; long-term CD8 + T M maintenance is associated with a pronounced increase of XCL1 production capacity; chemokines dominate the earliest stages of the CD8 + T M recall response because of expeditious synthesis/secretion kinetics (CCL3/4/5) and low activation thresholds (CCL1/3/4/5/XCL1); and T M chemokine profiles modulated by persisting viral Ags exhibit both discrete functional deficits and a notable surplus. Nevertheless, recall responses and partial virus control in chronic infection appear little affected by the absence of major T M chemokines. Although specific contributions of T M -derived chemokines to enhanced immune protection therefore remain to be elucidated in other experimental scenarios, the ready visualization of T M chemokine-expression patterns permits a detailed stratification of T M functionalities that may be correlated with differentiation status, protective capacities, and potential fates., (Copyright © 2020 by The American Association of Immunologists, Inc.)