Pathogenic Mechanisms In HIV Disease

Niaid Extramural Activities

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Abstract

The immune systems of patients with HIV infection are characterized by a decrease in the number of helper/inducer (CD4) T lymphocytes. Studies have demonstrated that intermittent infusions of the T cell derived cytokine IL-2 can lead to profound increases in the size of the CD4+ pool. The cells responsible for this increase are characterized by expression of the CD25 molecule, a characteristic of the recently described T regulatory subset of CD4+ T cells. A detailed analysis of the CD4+CD25+ cells seen in the setting of IL-2 therapy revealed that they were the product of peripheral expansion, rather than the generation of new cells from the thymus. They were found to represent a diverse family of cells with the ability to recognize a wide array of antigens. These cells were similar to T regulatory cells in that they expressed increased levels of the transcription factor foxP3, however different from these cells in that they had phenotypic characteristics of both naive and memory cells and only weak suppressive activity. These cytokine-expanded cells exhibited low rates of spontaneous cell death and may be responsible for sustained low rates of turnover in the CD4+ T cell pool. In other collaborative work, techniques were optimized for the measurement of the alpha chain of the IL-7 receptor (CD127) in preparation for clinical trials of this lymphocyte growth and survival factor. Decreased levels of CD127 were noted in the setting of delayed processing or freezing.