Search

To better understand anti-malaria protective immune responses, we examined the cellular mechanisms that govern protective immunity in a murine Plasmodium yoelii 17X NL (PyNL) re-infection model. Initially, we confirmed that immune B cells generated during a primary PyNL infection were largely responsible for protection from a second PyNL infection. Using the previously identified memory B cell markers CD80, PD-L2, and CD73, we found an increase in the frequency of CD80-PD-L2-CD73+ B cells up to 55 days after a primary PyNL infection and at 4–6 days following a second PyNL infection. Moreover, injection of enriched immune CD19+CD73+ B cells into nonimmune mice were significantly more protective against a PyNL infection than CD73- B cells. Interestingly, a substantial fraction of these CD73+ B cells also expressed IgM and granzyme B, a biomolecule that has been increasingly associated with protective responses against malaria. [ABSTRACT FROM AUTHOR]

Abstract: CD8+ T cells are important for resolution of HSV-2 lesions from the female genital epithelium. It is uncertain whether optimal clearance of viruses such as HSV-2 that cause a limited, non-systemic infection solely requires expression of effector functions by infiltrating CD8+ T lymphocytes, or if the clearance rate is reflective of the expression level of critical effector functions. To address this, CD8+ T cells from normal OT-I mice or OT-I mice deficient in IFNγ (IFNγ−/−) or the IFNγ receptor (IFNγR−/−) were activated in vitro in the presence of IFNγ or IL-4 to generate a series of effector populations (Tc1 and Tc2-like respectively) that secreted different levels of IFNγ and expressed different levels of HSV-specific cytolytic function. Compared with Tc1 cells, Tc2-like cells produced the type 2 cytokines IL-4 and IL-5, exhibited decreased IFNγ secretion, diminished proliferation in vitro, and decreased antigen-specific cytolysis in vivo. Clearance of an ovalbumin-expressing HSV-2 strain (HSV-2 tk− OVA) by adoptively transferred Tc2-like cells was delayed relative to Tc1 cell recipients. Because donor Tc2-like cells proliferated in vivo and infiltrated the infected genital epithelium similar to Tc1 cells, the diminished virus clearance by Tc2-like effector cells correlated with reduced expression of critical effector functions. Together, these results suggest that high level expression of protective T cell functions by effector T cells is necessary for optimal clearance of HSV-2 from the genital epithelium. These results have important implications for vaccines designed to elicit CD8+ T cells against viruses such as HSV-2 that infect the genital tract. [Copyright &y& Elsevier]