Department of Allergy and Infectious Disease Faculty Papers

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    Diagnostic performance of oral swabs for non-sputum based TB diagnosis in a TB/HIV endemic setting
    (2021) LaCourse, Sylvia; Seko, Evans; Wood, Rachel; Bundi, Wilfred; Ouma, Gregory; Agaya, Janet; Richardson, Barbra; John-Stewart, Grace; Wandiga, Steve; Cangelosi, Gerard
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    Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment
    (2001-02-15) Malhotra, Uma; Holte, Sarah; Dutta, Sujay; Berrey, M. Michelle; Delpit, Elizabeth; Koelle, David M.; Sette, Alessandro; Corey, Lawrence; McElrath, M. Juliana
    HIV-1–infected patients treated early with combination antiretrovirals respond favorably, but not all maintain viral suppression and improved HIV-specific Th function. To understand if genetic factors contribute to this variation, we prospectively evaluated over 18 months 21 early-treated patients stratified by alleles of class II haplotypes. All seven subjects with the DRB1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus suppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher mean lymphoproliferation and IFN-γ secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were identified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 haplotype, have an important impact on virologic and immunologic responses. The advantage of the haplotype may relate to selection of key HIV-1 Th1 epitopes in highly conserved regions with avid binding to class II molecules. Eliciting responses to the promiscuous epitope region may be beneficial in vaccine strategies.
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    mRNA expression profiles for Escherichia coli ingested by normal and phagocyte oxidase-deficient human neutrophils
    (2002-10-15) Staudinger, Benjamin J.; Oberdoerster, Michele A.; Lewis, Patrick J.; Rosen, Henry
    To gain a better understanding of bacterial responses to complex and hostile environments generated within the neutrophil phagosome, we estimated mRNA abundance, using genomic arrays, in Escherichia coli cells ingested by normal and phagocyte oxidase-deficient human neutrophils. Genes regulated by the oxidant sensing transcription factor OxyR were among those strongly induced upon phagocytosis by normal, but not oxidase-deficient, neutrophils. Several genes related to nitrogen metabolism, especially those regulated by the NtrC and NAC proteins and transcribed via the ς54 alternative sigma factor, were suppressed by both normal and oxidase-deficient neutrophils. A ΔoxyRS mutant strain of E. coli was significantly more susceptible than the parent strain to neutrophil-mediated killing, which suggests that OxyR-regulated gene products contribute a measure of resistance to neutrophil antimicrobial systems. The hypersusceptibility of the ΔoxyRS mutant was attenuated when oxidase-deficient neutrophils were employed, suggesting that much of the protection afforded by the OxyR regulon is against oxidative antimicrobial factors. Expression profiling of phagocytosed bacteria appears to provide useful information about conditions in the phagocytic vacuole and about bacterial defenses mounted in response to this hostile environment.
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    Expression of cutaneous lymphocyte-associated antigen by CD8+ T cells specific for a skin-tropic virus
    (2002-08-15) Koelle, David M.; Liu, Zhi; McClurkan, Christopher M.; Topp, Max S.; Riddell, Stanley R.; Pamer, Eric G.; Johnson, Andrew S.; Wald, Anna; Corey, Lawrence
    Virus-specific CD8+ T cells traffic to infected tissues to promote clearance of infection. We used herpes simplex virus type 2 (HSV-2) as a model system to investigate CD8+ T cell trafficking to the skin in humans. Using human leukocyte antigen (HLA) class I tetramers, we observed that HSV-specific CD8+ T cells in the peripheral blood expressed high levels of cutaneous lymphocyte-associated antigen (CLA). In contrast, CD8+ T cells specific for non–skin-tropic herpesviruses lacked CLA expression. CLA-positive HSV-2–specific CD8+ T cells had the characteristics of central memory cells, expressing CCR7, CD62L, and CD28, and they proliferated briskly in response to antigen. CLA is related to a functional E-selectin ligand, and both E-selectin and CLA-positive cells were detected in HSV-2–infected skin. HSV-2–specific T cells adhered to cells transfected with E-selectin. A higher proportion of HSV-specific CD8+ T cells recovered from herpes lesions express CLA compared with blood, consistent with a role for CLA in skin homing. To our knowledge, this is the first report of expression of tissue-specific adhesion-associated molecules by virus-specific CD8+ T cells. The evaluation of vaccines for skin and mucosal pathogens should include study of the induction of appropriate tissue-specific homing molecules.