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CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.

ABSTRACT: CCR7 is an important chemokine receptor that regulates T cell trafficking and compartmentalization within secondary lymphoid organs. However, the T cell-intrinsic role of CCR7 during infection in the spleen is not well understood. This study was designed to understand how CCR7-dependent localization and migration of CD8(+) T cells in different compartments of the spleen affected the primary and recall responses after infection. To this end, we used adoptive transfer of naive Ag-specific CD8 T cells (OT-I) that either lacked CCR7 or constitutively expressed CCR7 (CD2-CCR7) in mice that were subsequently infected i.v. with Listeria monocytogenes. We show that naive CCR7(-/-)CD8(+) T cells failed to enter the T cell zone, whereas CD2-CCR7 OT-I cells were exclusively confined to the T cell zones of the spleen. Surprisingly, however, CCR7(-/-) OT-I cells entered the T cell zones after infection, but the entry and egress migratory pattern of these cells was dysregulated and very distinct compared with wild-type OT-I cells. Moreover, CCR7-deficient OT-I cells failed to expand robustly when compared with wild-type OT-I cells and were preferentially skewed toward a short-lived effector cell differentiation pattern. Interestingly, CCR7(-/-), CD2-CCR7, and wild-type OT-I memory cells responded equally well to rechallenge infection. These results highlight a novel role of CCR7 in regulating effector CD8 T cell migration in the spleen and demonstrate differential requirement of CCR7 for primary and secondary CD8 T cell responses to infection.

SUBMITTER: Sharma N

PROVIDER: S-EPMC4655190 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.

Sharma Naveen N Benechet Alexandre P AP Lefrançois Leo L Khanna Kamal M KM

Journal of immunology (Baltimore, Md. : 1950) 20151023 11

CCR7 is an important chemokine receptor that regulates T cell trafficking and compartmentalization within secondary lymphoid organs. However, the T cell-intrinsic role of CCR7 during infection in the spleen is not well understood. This study was designed to understand how CCR7-dependent localization and migration of CD8(+) T cells in different compartments of the spleen affected the primary and recall responses after infection. To this end, we used adoptive transfer of naive Ag-specific CD8 T ce ...[more]

PMID: 26500349

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Project description:Introduction:Cue reactivity (CR) research has reliably demonstrated robust cue-induced responding among smokers exposed to common proximal smoking cues (eg, cigarettes, lighter). More recent work demonstrates that distal stimuli, most notably the actual environments in which smoking previously occurred, can also gain associative control over craving. In the real world, proximal cues always occur within an environment; thus, a more informative test of how cues affect smokers might be to present these two cue types simultaneously. Methods:Using a combined-cue counterbalanced CR paradigm, the present study tested the impact of proximal (smoking and neutral) + personal environment (smoking and nonsmoking places) pictorial cues, on smokers' subjective and behavioral CR; as well as the extent to which cue-induced craving predicts immediate subsequent smoking in a within-subjects design. Results:As anticipated, the dual smoking cue combination (ProxS + EnvS) led to the greatest cue-induced craving relative to the other three cue combinations (ProxS + EnvN, ProxN + EnvS, and ProxN ± EnvN), ps < .004. Dual smoking cues also led to significantly shorter post-trial latencies to smoke, ps < .01. Overall CR difference score (post-trial craving minus baseline craving) was predictive of subsequent immediate smoking indexed by: post-trial latency to smoke [B = -2.69, SE = 9.02; t(143) = -2.98, p = .003]; total puff volume [B = 2.99, SE = 1.13; t(143) = 2.65, p = .009]; and total number of puffs [B = .053, SE = .027; t(143) = 1.95, p = .05]. Conclusions:The implications of these findings for better understanding the impact of cues on smoking behavior and cessation are discussed. Implications:This novel cue reactivity study examined smokers' reactivity to combined proximal and distal smoking cues. Exposure to a combination of two smoking cues (proximal and environment) led to the greatest increases in cue-induced craving and smoking behavior compared to all other cue combinations. Further, the overall magnitude of cue-induced craving was found to significantly predict immediate subsequent smoking. This work provides new insight on how exposure to various cues and cue combinations directly affect smokers' craving and actual smoking behavior, as well as the relationship between those two indices of reactivity.

Dataset Information

CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.

Publications

CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.

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