Absence of Both IL-7 and IL-15 Severely Impairs the Development of CD8+ T Cell Response against Toxoplasma gondii

CD8+ T cells play an essential role in the protection against both acute as well as chronic Toxoplasma gondii infection. Although the role of IL-15 has been reported to be important for the development of long-term CD8+ T cell immunity against the pathogen, the simultaneous roles played by both IL-15 and related γ-chain family cytokine IL-7 in the generation of this response during acute phase of infection has not been described. We demonstrate that while lack of IL-7 or IL-15 alone has minimal impact on splenic CD8+ T cell maturation or effector function development during acute Toxoplasmosis, absence of both IL-7 and IL-15 only in the context of infection severely down-regulates the development of a potent CD8+ T cell response. This impairment is characterized by reduction in CD44 expression, IFN-γ production, proliferation and cytotoxicity. However, attenuated maturation and decreased effector functions in these mice are essentially downstream consequences of reduced number of antigen-specific CD8+ T cells. Interestingly, the absence of both cytokines did not impair initial CD8+ T cell generation but affected their survival and differentiation into memory phenotype IL-7Rαhi cells. Significantly lack of both cytokines severely affected expression of Bcl-2, an anti-apoptotic protein, but minimally affected proliferation. The overarching role played by these cytokines in eliciting a potent CD8+ T cell immunity against T. gondii infection is further evidenced by poor survival and high parasite burden in anti IL-7 treated IL-15−/− mice. These studies demonstrate that the two cytokines, IL-7 and IL-15, are exclusively important for the development of protective CD8+ T cell immune response against T. gondii. To the best of our knowledge this synergism between IL-7 and IL-15 in generating an optimal CD8+ T cell immunity against intracellular parasite or any other infectious disease model has not been previously reported

A role for antigen in the maintenance of immunological memory

The immune system has a memory that it exhibits in the enhanced and augmented responses the second time it meets an antigen. The memory is the result of a number of changes to the system brought about during the primary response. The most important of these changes is the formation of an expanded pool of antigenspecific memory cells. One of the enduring questions in immunology is how these memory cells are maintained for such long periods. Until about 10 years ago, memory cells were thought to be very long-lived cells that required little, if any, external input to keep them alive. This view arose not out of data showing long cellular lifespans, but from the observation that memory responses could be elicited many years after immunization or infection. It has been a common failure in thinking about immunological memory to imbue the individual cells with properties of the whole system. Around 10–12 years ago, a number of studies were published that highlighted the influence of antigen on the survival of memory cells. These studies indicated that although the antigen-specific clones were long-lived, the constituent memory cells were relatively short-lived and required continued antigenic stimulation (1–3). In the intervening period, the argument about antigen dependence has continued, and recent experiments have swung opinion back towards an antigenindependent view. In this article, I wish to argue that in reality, as opposed to experimental models, the role of antigen in memory maintenance is a very important one, and that antigen persistence might be a crucial asset for any vaccine