The Importance of CD11b+ Dendritic Cells in CD4+ T Cell Activation In Vivo

Control of Leishmania Major Infection in a Mouse Model of Cutaneous Leishmaniasis A murine model of cutaneous leishmaniasis, using needle inoculation of Leishmania major, represents perhaps the most widely used system to study the contrasting effects of Th1 versus Th2 immunity in disease control. One of the intriguing aspects of this disease model is that certain strains of mice, such as BALB/c and SWR/J, fail to control infection leading to progressive lesion development and systemic infection, whereas the majority of other mouse strains control infection at the local site of inoculation. Most humans infected with L. major manifest with self-healing lesions limited to the skin. Thus, the susceptible strains of mice represent an abnormal situation seen in rare patients who succumb to systemic infection with the cutaneous Leishmania species. The susceptibility of BALB/c mice to L. major is a multigenic phenomenon (1) in which both the T cell and the non-T cell compartments are impaired (2). It is generally accepted that a predominant IL-4 response is associated with disease progression whereas an IL-12/IFN-␥ –mediated Th1 response is associated with lesion resolution and control of parasite spread. However, recent evidence suggests that a transient Th2 response occurs in both resistant and susceptible strains of mice (3), but a sustained Th2 response is required for the development and progression of disease (for a review, see reference 4). Of importance in this regard are the abilities of the APCs in redirecting the early Th2 response toward a protective Th1 response. Two papers published in this issue by Filippi et al. (5) and by von Stebut and colleagues (6) address whether DCs and the factors secreted by these cells contribute to the susceptible versus resistant phenotypes after intradermal (i.d.) L. major challenge, and point to a selective role for the CD11b hi subset of DCs in this process (5). Identification of a Subset of Cutaneous DCs that Present Leishmania Antigens In Vivo. At the site of parasite inoculation , a number of distinct potential APCs are present including epidermal Langerhans cells, dermal DCs, and dermal macrophages. Within the epidermal layer are the Langerhans cells that are characterized by their unique in-tracellular organelles known as the Birbeck granules in which the Langerin molecule is expressed (7, 8). In response to stimulation, Langerhans cells emigrate in increased numbers from the epidermis to the draining LNs. This process is accompanied by the increase in their expression of …