3 research outputs found
T cell receptor-o deletion in human T cells
The immune system protects the body against pathogens such as bacteria,
viruses, fungi, and parasites, when they pass the first line of body defence such as
the skin or other epithelial and mucosal barriers.
After penetration into the body, micro-organisms encounter the second line of
defence. This concerns the so-called aspecitlc immune system, which consists of
phagocytes, such as macrophages and granulocytes, complement factors, and natural
killer cells. Generally, support by the third line of defence is needed, i.e. the socalled
specific irrunune system
Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection
Recent thymic emigrants can be identified by T cell receptor excision
circles (TRECs) formed during T-cell receptor rearrangement.
Decreasing numbers of TRECs have been observed with
aging and in human immunodeficiency virus (HIV)-1 infected
individuals, suggesting for thymic impairment. Here, we show
that in healthy individuals, declining thymic output will affect
the TREC content only when accompanied by naive T-cell division.
The rapid decline in TRECs observed during HIV-1 infection
and the increase following HAART are better explained not
by thymic impairment, but by changes in peripheral T-cell division
rates. Our data indicate that TREC content in healthy individuals
is only indirectly related to thymic output, and in HIV-1
infection is mainly affected by immune activation
In Psoriasis Lesional Skin the Type I Interferon Signaling Pathway Is Activated, whereas Interferon-α Sensitivity Is Unaltered
The epidermal phenotype as observed in psoriatic skin results from inflammation and abnormal proliferation and terminal differentiation of keratinocytes. Mice deficient for interferon regulatory factor-2, a repressor of interferon signaling, display psoriasis-like skin inflammation. The development of this phenotype is strictly dependent on type I interferon (interferon-α/β) signaling. The aim of this study was to assess the involvement of interferon-α/β in the pathogenesis of human psoriasis. In psoriatic skin, we measured an increased expression of components that play central and crucial roles in interferon-α/β signal transduction. Culturing keratinocytes or healthy skin biopsies with recombinant interferon-α stimulated this signaling pathway; however, this did not induce the expression of markers that are generally used to define the psoriasis phenotype. Furthermore, skin from psoriasis patients responded identically to interferon-α stimulation, demonstrating that psoriatic skin does not have an aberrant sensitivity to type I interferon. We conclude that in psoriatic lesional skin the type I interferon signaling pathway is activated, despite an unaltered interferon-α sensitivity. Our data furthermore show that type I interferon, in contrast to interferon-γ, does not act directly on keratinocytes to induce a psoriatic phenotype. Thus, if the observed activated type I interferon signaling is indeed functionally involved in the pathogenesis of psoriasis, its contribution might be indirect, putatively involving other cell types besides keratinocytes