Human T cells efficiently control RSV infection
Chandrav De, Raymond J. Pickles, Wenbo Yao, Baolin Liao, Allison Boone, Mingyu Choi, Diana M. Battaglia, Frederic B. Askin, Jason K. Whitmire, Guido Silvestri, J. Victor Garcia, Angela Wahl
Chandrav De, Raymond J. Pickles, Wenbo Yao, Baolin Liao, Allison Boone, Mingyu Choi, Diana M. Battaglia, Frederic B. Askin, Jason K. Whitmire, Guido Silvestri, J. Victor Garcia, Angela Wahl
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Research Article Immunology Virology

Human T cells efficiently control RSV infection

Abstract

Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in infants, immunocompromised individuals, and older individuals. There is an urgent need for effective antivirals and vaccines for high-risk individuals. We used 2 complementary in vivo models to analyze RSV-associated human lung pathology and human immune correlates of protection. RSV infection resulted in widespread human lung epithelial damage, a proinflammatory innate immune response, and elicited a natural adaptive human immune response that conferred protective immunity. We demonstrated a key role for human T cells in controlling RSV infection. Specifically, primed human CD8+ T cells or CD4+ T cells effectively and independently control RSV replication in human lung tissue in the absence of an RSV-specific antibody response. These preclinical data support the development of RSV vaccines, which also elicit effective T cell responses to improve RSV vaccine efficacy.

Authors

Chandrav De, Raymond J. Pickles, Wenbo Yao, Baolin Liao, Allison Boone, Mingyu Choi, Diana M. Battaglia, Frederic B. Askin, Jason K. Whitmire, Guido Silvestri, J. Victor Garcia, Angela Wahl

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Figure 5

Adoptively transfered primed autologous human CD4+ or CD8+ T cells control RSV replication in vivo.

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Adoptively transfered primed autologous human CD4+ or CD8+ T cells contr...
(A) Experimental diagram to evaluate RSV replication in LoM following adoptive transfer of primed autologous CD4+ and CD8+ T cells. LoM were challenged with RSV-Luc and then, 14 days later, transplanted with autologous CD4+ T cells (15 × 106), CD8+ T cells (15 × 106), or both CD4+ (7.5 × 106) and CD8+ (7.5 × 106) T cells isolated from RSV-infected human donor-matched BLT-L mice. RSV-infected LoM that did not receive cells served as a control for RSV replication. (B) Longitudinal analysis of RSV replication in LoM that received no cells (green boxes, n = 8 implants), CD8+ T cells (red boxes, n = 8 implants), CD4+ T cells (blue boxes, n = 8 implants), or both CD4+ and CD8+ T cells (purple boxes, n = 8 implants) as measured by bioluminescence signal (radiance [p sec–1 cm–2 sr–1] represented as total flux). Dashed line indicates threshold for bioluminescence detection. The median (horizontal line), upper and lower quartiles (box ends), and minimum to maximum values (whiskers) are shown. Statistical significance was compared with a 2-tailed Kruskal-Wallis test. P values were adjusted for multiple testing using the Benjamini, Krieger, and Yekutieli FDR method. (C) RSV antigen staining (brown) in the human lung implants of RSV-infected LoM 10 weeks after adoptive transfer of no cells, CD8+ T cells, CD4+ T cells, or both CD4+ and CD8+ T cells (n = 4 implants analyzed/group). Scale bars: 100 μm.