International Immunology Advance Access published online on June 1, 2007
International Immunology, doi:10.1093/intimm/dxm039
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The CD8 T cell response to vaccinia virus exhibits site-dependent heterogeneity of functional responses
Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street S.E., Minneapolis, MN, USA
Correspondence to: Correspondence to: M. F. Mescher; E-mail: mesch001{at}umn.edu
CD8 T cell responses to vaccinia virus (VV) and a virus-encoded ovalbumin peptide (OVAP) epitope were examined using adoptively transferred OT-I T cells. The results demonstrate that upon intra-peritoneal challenge with ovalbumin-expressing VV (VV-OVAP), OT-I T cell proliferation occurs initially in lymph nodes and spleens followed by migration of the divided cells to the peritoneal cavity. Massive clonal expansion occurs in response to both the virus and the virus-encoded ovalbumin (OVA) epitope, as demonstrated using low numbers of adoptively transferred cells, and the responding OT-I cells display marked site-dependent functional heterogeneity with respect to IFN-
and tumor necrosis factor-
(TNF-) production and granzyme B expression. OT-I cells responding to VV-OVAP develop the capacity to produce IFN- in response to antigen as they proliferate and differentiate. In marked contrast, naive OT-I cells rapidly produce TNF- upon antigen recognition, and this capacity declines as the cells proliferate in response to the virus, suggesting that this potent inflammatory cytokine may be important primarily during initiation of the response. At the peak of clonal expansion, a large fraction (30–60%) of the OT-I cells responding to the virus express high IL-7R levels, and the majority of these cells is subsequently lost. While high IL-7R expression may be necessary for a CD8 T cell to transition to memory, it is clearly not sufficient. Thus, OT-I cells responding to VV infection exhibit a high degree of heterogeneity within the responding population that differs depending on their anatomical location, despite the specificity and affinity of the TCR being identical on all of the cells.
Keywords: cell activation, cytotoxic T cells, viral infection
Transmitting editor: M. J. Bevan
Received 3 November 2006, accepted 7 March 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. L. Martin, M. D. Schwartz, S. C. Jameson, and Y. Shimizu Selective Regulation of CD8 Effector T Cell Migration by the p110{gamma} Isoform of Phosphatidylinositol 3-Kinase J. Immunol., February 15, 2008; 180(4): 2081 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Hammerbeck and M. F. Mescher Antigen Controls IL-7R{alpha} Expression Levels on CD8 T Cells during Full Activation or Tolerance Induction J. Immunol., February 15, 2008; 180(4): 2107 - 2116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Joshi and S. M. Kaech Effector CD8 T Cell Development: A Balancing Act between Memory Cell Potential and Terminal Differentiation J. Immunol., February 1, 2008; 180(3): 1309 - 1315. [Abstract] [Full Text] [PDF]
|
|