Chemokine Signatures of Pathogen-Specific T Cells II: Memory T Cells in Acute and Chronic Infection.

Abstract

Pathogen-specific memory T cells (TM) 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 TM 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 TM CD8+TM, and to a lesser extent CD4+TM, 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+TM serves as a unique functional imprint of prior antigenic experience; induced CCL1 production identifies highly polyfunctional CD8+ and CD4+TM subsets; long-term CD8+TM maintenance is associated with a pronounced increase of XCL1 production capacity; chemokines dominate the earliest stages of the CD8+TM recall response because of expeditious synthesis/secretion kinetics (CCL3/4/5) and low activation thresholds (CCL1/3/4/5/XCL1); and TM 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 TM chemokines. Although specific contributions of TM-derived chemokines to enhanced immune protection therefore remain to be elucidated in other experimental scenarios, the ready visualization of TM chemokine-expression patterns permits a detailed stratification of TM functionalities that may be correlated with differentiation status, protective capacities, and potential fates.

• Authors: Bennett Davenport, Jens Eberlein, Tom T Nguyen, Francisco Victorino, Verena van der Heide, Maxim Kuleshov, Avi Ma'ayan, Ross Kedl, Dirk Homann
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 205 Issue 8 Pg. 2188-2206 (10 15 2020) ISSN: 1550-6606 [Electronic] United States
• PMID: 32948682 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 by The American Association of Immunologists, Inc.

Chemical References

• Chemokines

Topics

• Acute Disease
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Chemokines (genetics, immunology)
• Chronic Disease
• Immunologic Memory
• Infections (genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout