Several studies have demonstrated genetic predisposition in non-shigatoxin-associated hemolytic uremic syndrome (HUS), involving regulatory proteins of the complement alternative pathway: Factor H (FH) and membrane co-factor protein (CD46). Regarding the observations of thrombotic thrombocytopenic purpura patients, in whom a von Willebrand factor protease (ADAMST-13) deficiency may be inherited or acquired secondary to IgG antibodies, it was speculated that HUS might occur in a context of an autoimmune disease with the development of anti-FH antibodies leading to an acquired FH deficiency. The presence of FH autoantibodies was investigated by an ELISA method using coated purified human FH in a series of 48 children who presented with atypical HUS and were recruited from French university hospitals. Anti-FH IgG antibodies were detected in the plasma of three children who presented with recurrent HUS. The anti-FH specificity was conserved by the Fab2 fraction. The plasma FH activity was found to be decreased, whereas plasma FH antigenic levels and FH gene analysis were normal, indicating that the presence of anti-FH antibodies led to an acquired functional FH deficiency. This report supports for the first time that HUS may occur in a context of an autoimmune disease with the development of anti-FHspecific antibody leading to an acquired FH deficiency. This new mechanism of functional FH deficiency may lead to the design of new approaches of diagnosis and treatment with a particular interest in plasma exchanges or immunosuppressive therapies.

The present study demonstrates that CD4 ؉ CD25 ؉ T cells, expanded in peripheral blood of HIV-infected patients receiving highly active antiretroviral therapy (HAART), exhibit phenotypic, molecular, and functional characteristics of regulatory T cells. The majority of peripheral CD4 ؉ CD25 ؉ T cells from HIV-infected patients expressed a memory phenotype. They were found to constitutively express transcription factor forkhead box P3 ( IntroductionHIV infection is mainly associated with a progressive decrease in the number of CD4 ϩ T lymphocytes and defective CD4-specific and CD8-specific T-cell responses against HIV and other pathogens. It has been demonstrated that highly active antiretroviral therapy (HAART) results in reduced HIV-1 replication, increased CD4 cell counts in most treated patients, and progressive but incomplete recovery of CD4 ϩ T-cell functions. [1][2][3][4] Thus, treatment of chronic HIV infection does not result in most cases in a full recovery of HIV-specific helper and cytotoxic T lymphocyte (CTL) responses (reviewed in Sakaguchi et al 5 ).Recently, a CD4 ϩ T-cell subset with regulatory properties has been characterized in humans several years after their discovery in mice. [6][7][8][9][10] These cells, named "regulatory T" (Treg) cells express the ␣ chain of the interleukin 2 (IL-2) receptor (CD25) and can inhibit the proliferation of CD4 ϩ and CD8 ϩ T lymphocytes both in vitro and in vivo. 9,11 It has been demonstrated that transfer of such cells can protect neonatally thymectomized mice from autoimmune diseases, whereas their depletion results in the development of systemic autoimmune diseases. [12][13][14] Moreover, alloantigen-induced CD4 ϩ CD25 ϩ regulatory T cells were reported to prevent rejection initiated by CD4 ϩ cells in both organ and bone marrow transplantation. 15,16 Although CD25 is usually considered as an activation marker, it has been shown that CD4 ϩ CD25 ϩ lymphocytes do not proliferate in response to polyclonal, allogenic, or antigen-specific stimulation 8,9,17 but require activation through their T-cell receptor (TCR) to exert their suppressive function. Their anergic state could be partially reversed by IL-2 and IL-15. 9 Besides CD4 ϩ CD25 ϩ regulatory T cells, 2 other types of CD4 ϩ cells with suppressive function have been described: type 1 T regulatory (Tr1) cells 18 and T-helper 3 (Th3) cells. 19 Tr1 cells were reported to suppress the immune response via the secretion of the immunosuppressive cytokines IL-10 and transforming growth factor ␤ (TGF-␤). The mechanism by which CD4 ϩ CD25 ϩ T cells mediate suppression seems to require direct cell-cell contact. Levings et al 19 have recently demonstrated, at the clonal level, that Tr1 and CD4 ϩ CD25 ϩ T cells are distinct subsets of regulatory T cells and that the suppression mediated by CD4 ϩ CD25 ϩ T cells is partially dependent on TGF-␤.In healthy individuals, the CD4 ϩ CD25 ϩ T-cell subset represents 5% to 10% of peripheral CD4 ϩ T cells and is characterized by the constitutive expression of CD152 (CTL-associate...

HIV infection results in CD4

Immunologic response after 6 months of HAART indicates a favorable clinical outcome in HIV-infected patients regardless of virologic response. This suggests that both immunologic and virologic markers should be used in clinical practice to evaluate treatment response.

No abstract

Infection with the human immunodeficiency virus HIV-1 is associated with the expansion of a CD14lowCD16high monocyte subset in peripheral blood. This subset, which represents a minor subpopulation of monocytes in healthy individuals, increases during HIV infection and, in patients with AIDS, may represent up to 40% of the total circulating monocyte cell population. The CD14lowCD16high circulating monocytes co-express MAX.1, p150,95 and HLA-DR which are typical of tissue macrophage markers. These cells also express higher levels of intracellular interleukin (IL)-1 alpha and tumor necrosis factor (TNF)-alpha than the CD14highCD16low monocyte population from the same patients. The CD14lowCD16high cells also express low levels of CD35, CD11a and CD4 in common with normal monocytes. When cultured in vitro, monocytes from HIV-seropositive individuals differentiated within a few hours into an elongated fibroblastoid shape characteristic of migratory cells. Our results suggest that the expansion of the CD14lowCD16high monocyte subset, which produce high amount sof TNF-alpha and IL-1 alpha, may participate in the immune dysfunction observed during HIV infection.

Natural regulatory T cells (Tregs) participate in responses to various chronic infections including HIV. HIV infection is associated with a progressive CD4 lymphopenia and defective HIV-specific CD8 responses known to play a key role in the control of viral replication. Persistent immune activation is a hallmark of HIV infection and is involved in disease progression independent of viral load. The consequences of Treg expansion, observed in HIV infection, could be either beneficial, by suppressing generalized T-cell activation, or detrimental, by weakening HIV-specific responses and thus contributing to viral persistence. The resulting balance between Tregs contrasting outcomes might have critical implications in pathogenesis. Topics covered in this review include HIV-induced alterations of Tregs, Treg cell dynamics in blood and tissues, Treg-suppressive function, and the relationship between Tregs and immune activation. This review also provides a focus on the role of CD39+ Tregs and other regulatory cell subsets. All these issues will be explored in different situations including acute and chronic infection, antiretroviral treatment-mediated viral control, and spontaneous viral control. Results must be interpreted with regard to both the Treg definition used in context and to the setting of the disease in an attempt to draw clearer conclusions from the apparently conflicting results.

What is already known about this topic? Coronavirus disease 2019 has a mild disease course in children and adolescents. Chronic respiratory conditions, including asthma, have been suggested as risk factors; however, asthma in children is highly variable in both triggers and severity.What does this article add to our knowledge? During the pandemic, pediatric asthma services limited consultations and established virtual clinics. However, respondents perceived their patients' asthma control to be retained or even improved, while treatment adherence was considered increased. Children with asthma were not disproportionately affected by coronavirus disease 2019.How does this study impact current management guidelines? Trigger avoidance and treatment adherence can rapidly improve asthma control in children, even under lockdown pressure. Children/adolescents with asthma do not appear to need additional prophylactic measures from coronavirus disease 2019 when asthma is well-treated.