Myogenic precursor cells in craniofacial muscles.

Craniofacial skeletal muscles (CskM), including the masticatory (MM), extraocular (EOM) and laryngeal muscles (LM), have a number of properties that set them apart from the majority of skeletal muscles (SkM). They have embryological origins that are distinct from musculature elsewhere in the body, they express a number of immature myosin heavy chain isoforms and maintain increased and distinct expression of a number of myogenic growth factors and their receptors from other adult SkMs. Furthermore, it has recently been demonstrated that unlike limb SkM, normal adult EOM and LM retain a population of activated satellite cells, the regenerative cell in adult SkM. In order to maintain this proliferative pool throughout life, CSkM may contain more satellite cells and/or more multipotent precursor cells that may be more resistant to apoptosis than those found in limb muscle. A further exciting question is whether this potentially more active muscle precursor cell population could be utilized not only for SkM repair, but be harnessed for repair or reconstruction of other tissues, such as nervous tissue or bone. This is a highly attractive speculation as the innate regenerative capacity of craniofacial muscles would ensure the donor tissue would not have compromised future function.

Generation of anergic and potentially immunoregulatory CD25+CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen.

Immunoregulatory CD25(+)CD4 T cells are thought to arise from the thymus as a distinct lineage of CD4 T cells specific for self Ags. We used the DO11.10 TCR transgenic adoptive transfer system to show that cells of similar phenotype may also arise in the course of peripheral tolerance induction. Such cells emerged within 1 wk following Ag exposure and correlated negatively with the number of initial cell divisions. Limiting i.v. Ag dose or using an oral tolerance protocol yielded the greatest numbers of Ag-specific CD25(+)CD4 T cells. In contrast, immunogenic Ag exposure in the presence of an adjuvant did not lead to emergence of CD25(+)CD4 T cells. The profound anergic phenotype of these cells and their potential immunoregulatory properties make them an especially desirable population to induce in the course of immunotherapy in numerous clinical settings. This experimental system may be useful in future studies designed to optimize immunologic tolerance induction.