Biomedical subjects

Joanne M Fraser

Publications and source records attributed to Joanne M Fraser.

3 recordsLinked to original sources

PubMed2006

Abortive activation precedes functional deletion of CD8+ T cells following encounter with self-antigens expressed by resting B cells in vivo.

InsHA mice express the haemagglutinin (HA) protein from influenza virus A/PR/8 H1N1 (PR8) as a self antigen on pancreatic islet beta cells. We have utilized these mice to investigate the ability of resting B cells expressing Kd to induce self-tolerance among naive KdHA-specific clone 4 CD8+ T cells. Adoptive transfer of KdHA-peptide-pulsed resting B cells into clone 4-->InsHA recipients resulted in the activation and proliferation of clone 4 CD8+ T cells throughout the peripheral lymphoid tissues. Significantly, proliferation was not associated with the acquisition of T cell effector function; as evidenced by a lack of interferon-gamma production and the complete absence of any autoimmune pathology even after immunization of recipient mice with PR8. These data demonstrate that resting B cells pulsed with self-epitopes can induce abortive activation of potentially self-reactive naive CD8+ T cells resulting in their functional deletion from the peripheral T-cell repertoire in the absence of any associated autoimmunity.

Adoptive Transfer↗

PubMed2004

A causal link between lymphopenia and autoimmunity.

It is well recognized that the composition of the mature T cell population is subject to strict homeostatic control. The TCR repertoire and relative proportions of various T cell subsets are established in the thymus, and continue to be shaped and regulated in the periphery. As the thymic function declines, peripheral homeostatic mechanisms assume increasing importance. Indeed, loss of thymic function does not lead to progressive decline of T cell numbers because peripheral mechanisms ensure that the size of the T cell population is maintained due to proliferation of residual cells. However, our current understanding of the basic mechanisms of 'homeostatic' or lymphopenia-induced proliferation suggests that this drive to maintain population size may be accompanied by loss of TCR diversity and emergence of auto-reactive effector T cells. This prediction is supported by experimental and clinical evidence. This consideration is important because lymphopenia is seen commonly in clinical practice as a consequence of viral infections, or medical treatment of cancer, autoimmunity, and graft rejection. Lymphopenia may be a simple link between viral infections and autoimmunity, and may be one reason for common failure of very potent, but non-specific, immunosuppressive drugs in current clinical use.

Animals↗

PubMed2003

New therapy update--A unique combination formulation in the treatment of inflammatory acne.

Duac Topical Gel (clindamycin 1%-benzoyl peroxide 5%) is a uniform, aqueous gel manufactured under the US Food and Drug Administration (FDA) Current Good Manufacturing Practice (cGMP) regulations and controls, which ensure that consistent product is delivered to the patient every time. Since the product is premixed, the patient does not have to wait for mixing or compounding by the pharmacist. The active ingredients have been shown to be stable for 60 days at room temperature, so that neither the patient nor the physician needs to store the product in the refrigerator. When kept at temperatures of 2 degrees C to 8 degrees C, the product is stable for 2 years. In a clinical study of 358 subjects with moderate to moderately severe acne vulgaris, once-daily treatment with clindamycin 1%-benzoyl peroxide 5% for 11 weeks reduced inflammatory lesions by 53% and noninflammatory lesions by 25%. Good or excellent global response was experienced in 50% of subjects. Overall tolerance ratings were good to excellent in 99% of subjects, and, except for mild to moderate expected local reactions, there were no adverse events related to treatment.

Acne Vulgaris↗