TY - JOUR
T1 - IL-15 regulates both quantitative and qualitative features of the memory CD8 T cell pool
AU - Sandau, Michelle M.
AU - Kohlmeier, Jacob E.
AU - Woodland, David L.
AU - Jameson, Stephen C.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Memory T cells are critical for immunity to various intracellular pathogens. Recent studies have indicated that CD8 secondary memory cells, induced by prime-boost approaches, show enhanced protective function compared with primary memory cells and exhibit phenotypic and functional characteristics that distinguish them from primary memory cells. However, little is known about the cytokine requirements for generation and maintenance of boosted memory CD8 T cells. We studied the role of IL-15 in determining the size and composition of the secondary (2° ) memory CD8 T cell pool induced by Listeria monocytogenes infection in mice. Following boosting, IL-15-deficient animals failed to generate a subset of CD8 effector memory cells, including a population of IL-7Rαlow cells, which were prominent among secondary memory cells in normal mice. IL-15 deficiency also resulted in changes within the IL-7RαhighCD62Llow subset of 2° memory CD8 T cells, which expressed high levels of CD27 but minimal granzyme B. In addition to these qualitative changes, IL-15 deficiency resulted in reduced cell cycle and impaired Bcl-2 expression by 2° memory CD8 T cells, suggesting a role for IL-15 in supporting both basal proliferation and survival of the pool. Analogous qualitative differences in memory CD8 T cell populations were observed following a primary response to Sendai virus in IL-15-/- animals. Collectively, these findings demonstrate that IL-15 plays an important role in dictating the composition rather than simply the maintenance of the CD8 memory pool.
AB - Memory T cells are critical for immunity to various intracellular pathogens. Recent studies have indicated that CD8 secondary memory cells, induced by prime-boost approaches, show enhanced protective function compared with primary memory cells and exhibit phenotypic and functional characteristics that distinguish them from primary memory cells. However, little is known about the cytokine requirements for generation and maintenance of boosted memory CD8 T cells. We studied the role of IL-15 in determining the size and composition of the secondary (2° ) memory CD8 T cell pool induced by Listeria monocytogenes infection in mice. Following boosting, IL-15-deficient animals failed to generate a subset of CD8 effector memory cells, including a population of IL-7Rαlow cells, which were prominent among secondary memory cells in normal mice. IL-15 deficiency also resulted in changes within the IL-7RαhighCD62Llow subset of 2° memory CD8 T cells, which expressed high levels of CD27 but minimal granzyme B. In addition to these qualitative changes, IL-15 deficiency resulted in reduced cell cycle and impaired Bcl-2 expression by 2° memory CD8 T cells, suggesting a role for IL-15 in supporting both basal proliferation and survival of the pool. Analogous qualitative differences in memory CD8 T cell populations were observed following a primary response to Sendai virus in IL-15-/- animals. Collectively, these findings demonstrate that IL-15 plays an important role in dictating the composition rather than simply the maintenance of the CD8 memory pool.
UR - http://www.scopus.com/inward/record.url?scp=73949111444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73949111444&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0803355
DO - 10.4049/jimmunol.0803355
M3 - Article
C2 - 19949092
AN - SCOPUS:73949111444
SN - 0022-1767
VL - 184
SP - 35
EP - 44
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -