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The development of naive CD4 T cells into type 1 or type 2 Th cells has been extensively analyzed in the mouse. Using neonatal CD4 T lymphocytes as a source of human naive cells, we report that these cells may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines. After 3 days of stimulation with anti-CD3 mAb(More)
New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme(More)
Benzothiazinones (BTZs) form a new class of potent antimycobacterial agents. Although the target of BTZs has been identified as decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), their detailed mechanism of action remains obscure. Here we demonstrate that BTZs are activated in the bacterium by reduction of an essential nitro group to a nitroso(More)
18 cloned T cell lines reactive with Borrelia burgdorferi proteins, all CD3+4+8-TCR-alpha/beta+ and restricted by HLA class II proteins, were isolated from four patients with chronic Lyme arthritis. Analysis of these T cell clones indicated that the T cell response to the Lyme disease spirochete is not oligoclonally restricted; yet all produced the same(More)
Nonreplicating or dormant cells of Mycobacterium tuberculosis constitute a challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic resistance to most drugs. Here, we propose a simple model for testing drugs against nongrowing cells that exploits the 18b strain of M. tuberculosis, a streptomycin (STR)-dependent mutant. Optimal(More)
We describe the isolation of a cDNA that encodes human lymphotactin (Ltn), a new class of lymphocyte-specific chemokine. Human Ltn shows similarity to some members of the C-C chemokine family but has lost the first and third cysteine residues that are characteristic of the C-C and C-X-C chemokines. Ltn is chemotactic for lymphocytes but not for monocytes, a(More)
Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find antimycobacterial scaffolds, we screened a kinase inhibitor library of more than 12,000 compounds using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis,(More)
Cloned T lymphocytes reactive with Borrelia burgdorferi proteins were isolated from a patient with chronic Lyme arthritis. All of the T cell clones which proliferated in response to Borrelia proteins were CD3 + CD4 + CD8 - TCR alpha beta + and HLA-DR restricted. One T cell clone (GN30) exhibited HLA-DR-restricted cytotoxic activity against(More)
Cloned human CD4+ T cell lines specific for the house dust mite Dermatophagoides pteronyssinus were used to map minimal T cell activation-inducing epitopes on the Group I allergen in D. pteronyssinus extracts (Der p I) molecule. Most of these Der p I-specific T cell clones expressed different TCR V alpha and V beta gene products. Using recombinant deletion(More)
The synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-Cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin N and O is reported. These compounds were evaluated in vitro against four parasites(More)