Item Details

abstract

Dendritic cells (DC) bridge innate and adaptive immunity as the effective activators of naïve T cells. Three signals from DC contribute to the CD8+ T cell activation and acquisition of effector function: 1. peptide/MHC, 2. costimulatory molecules (eg. CD80, CD86), and 3. secreted cytokines (e.g. IL-12, type I IFN). The first two signals require direct DC and T cell contact. In contrast, the third signal could be obtained from the local environment. In this study, the DC in the MLN are divided into four subsets based on the expression of CD8 and CD103 molecules. Among the four subsets, the two CD103+ DC subsets are from the airway while the CD8+ CD103- DC are lymph node resident. xi The CD8- CD103- DC subset is a mixed population, including CD103- CD11b+ lung parenchyma DC, CD8- lymph node resident DC, pDC and monocytic Gr-1+ DC. This division allows us to study the subsets important for the naïve CD8+ T cell priming: CD103+ DC and CD8+ lymph node resident DC. We utilized intranasal infection of BALB/c mice with paramyxovirus recombinant Simian Virus 5(rSV5-eGFP-p60) as a model to explore the behavior of these four DC subsets in vivo with regard to regulation of costimulatory molecules and cytokine secretion. We found that the number of mature DC, defined as CD80 and CD86 double positive DC, increased over time following infection, reached the maximum at day 2 post infection (p.i.) and rapidly decreased in both CD103+ DC subsets while that of the two CD103- DC subsets continued to increase from day 1 to day 4 p.i. Specifically, the mature CD103- DC increased significantly from day 3 to day 4, following the peak of CD103+ DC cell number. The number of IL-12p40 producing DC increased in a similar pattern in each DC subset following infection. Interestingly, we found that all the DC subsets were able to undergo full maturation, which means the upregulation of both CD80 and CD86 expression. This result was reported in BMDC in response to productive rSV5 infection at M.O.I of 50 in vitro. We proposed that the complex vivo inflammatory environment, which includes other cell populations and inflammatory cytokines, were responsible for the full maturation of both CD103+ DC and CD103- DC. Specifically, we proposed a model which described the direct or indirect interaction between lung migrant DC and lymph node resident DC contributed to the induction of the maturation of the latter population. xii These data provided new insights into the control of the innate immune response in response to viral infection and might reveal novel understanding of the initiation of anti-viral adaptive immune response.

subject

DC maturation

innate immunity

viral infection

SV5

contributor

Zha, Jingying (author)

High, Kevin (committee chair)

Alexander-Miller, Martha (committee member)

Hiltbold, Elizabeth (committee member)

Grayson, Jason (committee member)

Parks, Griffith (committee member)

date

2009-08-11T15:54:08Z (accessioned)

2010-06-18T18:56:50Z (accessioned)

2009-08-11T15:54:08Z (available)

2010-06-18T18:56:50Z (available)

2009-08-11T15:54:08Z (issued)

degree

Microbiology & Immunology (discipline)

identifier

http://hdl.handle.net/10339/14652 (uri)

language

en_US (iso)

publisher

Wake Forest University

rights

Release the entire work for access only to the Wake Forest University system for one year from the date below. After one year, release the entire work for access worldwide. (accessRights)

title

Respiratory infection with the paramyxovirus SV5 results in maturation and cytokine secretion in CD103- and CD103+ dendritic cell subsets.

type

Thesis