The influence of macrophage inflammatory protein‐1α on protective immunity mediated by antiviral cytotoxic T cells

Abstract

SUMMARYMacrophage in¯ammatory protein 1a (MIP-1a), a member of the CC-chemokine subfamily, is known to induce chemotaxis of a variety of cell types in vivo. Although the role of MIP-1a in in¯ammatory responses generated following primary infection of mice with many different pathogens has been characterized, the in¯uence of this chemokine on the generation of antigen-speci®c T-cell responses in vivo is less well understood. This is important, as virus-speci®c CD8T lymphocytes (CTL) play a crucial role in defence against viral infections, both acutely and in the long term. In this study, we compared the ability of wild-type and MIP-1a-de®cient (MIP1aÀ/À) mice to mount CTL responses speci®c for the immunodominant epitope derived from in¯uenza nucleoprotein (NP366±374). In¯uenza-speci®c CTL responses were compared with respect to frequency, cytotoxic activity and ability to clear subsequent infections with recombinant vaccinia viruses expressing the in¯uenza NP. The results indicate that antiviral CTL generated in MIP-1aÀ/À mice are slightly impaired in their ability to protect against a subsequent infection. However, impaired in vivo CTL-mediated antiviral protection was found to be associated with reduced cytotoxicity rather than with a failure of the CTL to migrate to peripheral sites of infection.

CD62L (L-Selectin) Down-Regulation Does Not Affect Memory T Cell Distribution but Failure to Shed Compromises Anti-Viral Immunity

“…2C). The numbers of NP68-specific CD8 T cells detectable during primary infection were lower than those reported using HKx31 strain of influenza, particularly in the lungs (23), although the total number of CD8 T cells and the frequency of NP68 tetramer binding CD8 cells were similar to those previously reported by us for H17 (19,20) and for the HKx31 strain (24). To increase the yield of memory CD8 T cells from solid organs we employed collagenase digestion before cell isolation.…”

“…with 5 ϫ 10 6 PFU. Ovaries were removed 5 or 8 days later, and a single ovary from each mouse analyzed for rVV titers, as described previously (19). The remaining ovaries, as well as OdLN and spleen were harvested for immunostaining and in vitro CTL assays.…”

“…Spleen cells harvested from influenza virus infected mice at day 8, or from rVVNPP challenged influenza-immune mice at day 5, were plated at 4 ϫ 10 6 cells/well in RPMI 1640 supplemented with 10% FCS (RPMI 10) and cocultured with 1 ϫ 10 Ϫ6 M NP68 peptide (ASNENMDAM; Invitrogen) pulsed irradiated splenocytes in 24-well plates, as described previously (19). On day 5, cells from 4 wells were collected, washed, and resuspended in 600 l of RPMI 10.…”

CXCR3–/– mice mount an efficient Th1 response but fail to control Leishmania major infection

“…Recent studies have shown that chemokines play a critical role in the development of innate as well as acquired immunity against a variety of viruses, bacteria, fungi, and parasites [9][10][11]. The protective role of chemokines has been attributed to their ability to activate leukocytes and facilitate their recruitment to the site of infection [12,13].…”

Definition of Key Variables for the Induction of Optimal NY-ESO-1–Specific T Cells in HLA Transgene Mice

“…5B, 5C) (38)(39)(40). Moreover, CCL3 has been shown to have adjuvant effects on CD8 + T cell priming, to increase CD8 + T cell effector functions, and to be involved (together with other chemokines) in recruiting CD8 + T cells to inflamed sites (39,(41)(42)(43). Although CCL3 and CCL4 both bind to CCR5, the former, but not the latter, also binds to CCR1, which may account for their diverging biological effects (36,39).…”