CD8(+) T cells are a biologically relevant source of macrophage inflammatory protein-1 alpha in vivo

Chemokines are small proteins that direct the migration of leukocytes to in flammatory foci, Many cell types, including macrophages, fibroblasts, endot helial cells, and lymphocytes, produce chemokines in vitro, but biologicall y relevant sources of chemokines in vivo have not been wed characterized, T o investigate the pertinent sources of macrophage inflammatory protein-1 al pha (MIP-1 alpha) in vivo, we used MIP-1 alpha-deficient (MIP-1 alpha(-/-)) mice as donors and as recipients in adoptive transfer experiments after a lethal infection with Listeria monocytogenes (LR;I). Unexpectedly, we found that the production of MIP-1 alpha by CD8(+) T cells was critical in this system, as the cells from MIP-1 alpha(-/-) mice primed with LM were signifi cantly less effective in protecting naive mice against a lethal infection b y LM than were the CD8+ T cells from wild-type (wt) mice. This requirement for donor T cell production of MIP-1 alpha was confirmed by the observation that wt donor T cells do not mediate protection when coadministered with a n anti-MIP-1 alpha polyclonal antiserum. Production of MIP-1 alpha by the r ecipient mice was not required for protection, because wt and MIP-1 alpha(- /-) recipients were equally well protected by wt T cells, A 2- to 3-fold de crease in the number of transferred lymphocytes was seen in the spleens of mice receiving T cells from MIP-1 alpha(-/-) mice compared with those recei ving wt T cells. In addition, CD8(+) T cells from MIP-1 alpha(-/-) mice had a reduced ability to kill LM-infected target cells in vitro. These finding s demonstrate that T cell production of MIP-1 alpha is required for clearan ce of an intracellular pathogen in vivo.