Influenza virus is responsible for approximately 36,000 deaths per year in the U.S. Memory CD8+ T cells in the lung airways can play an important role in the control of secondary influenza virus infections. Recently, we demonstrated a strong non-specific recruitment of memory T cells into the lung airways following either heterologous, or homologous, respiratory virus infection. We hypothesize that this non-specific recruitment of memory cells is a component of the normal recall response in the lung airways. However, the factors that control this recruitment remain unclear.
In aim 1, I propose to further examine the requirements for nonspecific recruitment of memory T cells into the lung airways by determining: 1) whether the efficacy of this recruitment declines over time, 2) whether CD1 la is required for non-specific recruitment of memory T cells and 3) whether recruitment is reduced in the absence of IL-7 and/or IL-15. Although we demonstrated that non-specific recruitment occurred in both heterologous and homologous respiratory virus infections, the survival and function of these recruited cells in the presence or absence of cognate antigen remains unclear.
Aim 2, I will address 1) whether cognate antigen impacts the survival of these recruited cells. 2) whether these early recruited memory cells contribute to protection following respiratory virus challenge. Together, these studies will further our knowledge of mechanisms of non-specific memory cell recruitment and function into the lung airways. ? ?
| Ely, Kenneth H; Roberts, Alan D; Kohlmeier, Jacob E et al. (2007) Aging and CD8+ T cell immunity to respiratory virus infections. Exp Gerontol 42:427-31 |
| Ely, Kenneth H; Ahmed, Mushtaq; Kohlmeier, Jacob E et al. (2007) Antigen-specific CD8+ T cell clonal expansions develop from memory T cell pools established by acute respiratory virus infections. J Immunol 179:3535-42 |
| Hikono, Hirokazu; Kohlmeier, Jacob E; Takamura, Shiki et al. (2007) Activation phenotype, rather than central- or effector-memory phenotype, predicts the recall efficacy of memory CD8+ T cells. J Exp Med 204:1625-36 |
| Ely, Kenneth H; Cookenham, Tres; Roberts, Alan D et al. (2006) Memory T cell populations in the lung airways are maintained by continual recruitment. J Immunol 176:537-43 |
| Roberts, Alan D; Ely, Kenneth H; Woodland, David L (2005) Differential contributions of central and effector memory T cells to recall responses. J Exp Med 202:123-33 |
