IntroductionA progressive reduction in CD4 ϩ T-helper lymphocytes is the main feature of HIV infection and leads to a depression in adaptive immunity. 1 Innate immunity is also important in the host response to HIV infection and can be impaired during the course of this infection. Dendritic cells (DCs) can promote HIV transmission, [2][3][4][5] and DC function 6 and number 7 decline with HIV infection. The effector functions of monocytes and macrophages, including phagocytosis and intracellular oxidative responses, can be found decreased in HIV-infected subjects 8,9 and in cultured cells in the presence of HIV. [10][11][12][13] Superoxide production by neutrophils 14 as well as natural killer cell function as measured by the lymphokineactivated killer activity and responsiveness to interferon-␣ (IFN-␣) 15,16 have been shown to be defective in HIV-infected subjects.An important part of the innate defense against virus is the production of the type I IFNs, IFN-␣, and IFN-␤. 17 IFN-␣/␤ not only directly inhibit HIV replication, 18-20 but also have important adjuvant effects on a variety of immune cell types, such as monocytes, natural killer cells, 21 and T cells. [22][23][24][25][26] The in vitro type I IFN production by total peripheral blood mononuclear cells (PBMCs) was shown to be impaired during the course of HIV infection, and this impairment was associated with the occurrence of opportunistic infections. 27,28 CD4 ϩ CD11c Ϫ lineage marker Ϫ type 2 DC precursors (pre-DC2) were recently shown to be the natural IFN-␣/␤-producing cells in human blood. 29,30 IPCs produce up to 1000 times more IFN-␣ than any other blood cell type in response to viral stimulation. 29 Whether this impairment of IFN-␣/␤ production in HIV-infected individuals is due to a functional defect or to a reduction in number of IPCs is not known.In this study, we show that blood IPCs are severely decreased in AIDS patients but increased in asymptomatic long-term survivors (LTSs). The drop in IPC number and a decrease in their induced IFN production are associated with the presence of opportunistic infections and active Kaposi sarcoma. Our findings bring a new insight into the physiopathology of HIV infection and identify the IPC count as a new parameter to monitor the status of the immune system of HIV-infected subjects. Patients, materials, and methods HIV-infected subjectsFifty-four HIV-infected subjects were recruited from 3 centers: the University of California at San Francisco (UCSF), the San Francisco General Hospital, and the Hospices Civils de Lyon, France. This study was approved by the Committee for Human Research, UCSF. Subjects were enrolled consecutively, and the only inclusion criterion was a confirmed HIVpositive serology and a written informed consent. The following conditions, which can nonspecifically affect blood cell counts, were used as exclusion criteria: previous cytotoxic chemotherapy, splenectomy, hypersplenism, and blood transfusion within the past 4 weeks. After inclusion, a full medical history was taken and physic...

Drug allergic reactions presenting as maculo-papular exanthema (MPE) are mediated by drug-specific T cells. In this study, the frequency of circulating specific T cells was analyzed by interferon-gamma (IFN-gamma) enzyme-linked immunospot assay in 22 patients with an allergic MPE to amoxicillin (amox). Amox-specific circulating T cells were detected in 20/22 patients with frequencies ranging from 1 : 8000 to 1 : 30 000 circulating leucocytes. No reactivity was observed in 46 control patients, including 15 patients with immunoglobulin E-mediated allergy to amoxicillin, 11 patients with a history of drug-induced MPE but tolerant to amoxicillin and 20 healthy individuals. Furthermore, amox-specific T cells were still detectable several years after the occurrence of the allergic reaction even after strict drug avoidance. Finally, analysis of drug-specific T cells in one patient allergic to ticarcillin (a penicillin antibiotic distinct from amox) revealed the presence of IFN-gamma-producing T cells reactive to ticarcillin and several other betalactam antibiotics, suggesting that the IFN-gamma ELISPOT assay is able to detect T cell cross-reactivity against chemically related drugs. These findings confirm that drug-induced MPE is associated with the presence of specific T cells in blood and further suggest that the IFN-gamma ELISPOT is a sensitive assay which could improve the diagnosis of betalactam allergy.