Ras-associated small GTPase 33A, a novel T cell factor, is down-regulated in patients with tuberculosis.
Ras-associated small GTPases (Rabs) are specific regulators of intracellular vesicle trafficking. Interference with host cell vesicular transport is a hallmark of many intracellular pathogens, including the notable example Mycobacterium tuberculosis. We performed, by quantitative polymerase chain reaction, gene-expression analyses for selected Rab molecules in peripheral-blood mononuclear cells from patients with tuberculosis (TB) and healthy control subjects, to identify candidate genes that are critically involved in the host immune response. Comparison revealed significant differences in the expression of genes for Rab13, Rab24, and Rab33A. Rab33A gene expression was down-regulated in patients with TB and was predominantly expressed in CD8+ T cells. We excluded possible influences of differences in T cell percentages between the 2 study groups, demonstrating that Rab33A gene expression changes on the single-cell level. In vitro, Rab33A RNA expression was induced in T cells on activation and by dendritic cells infected with M. tuberculosis. Our findings identify Rab33A as a T cell regulatory molecule in TB and suggest its involvement in disease processes.
Jacobsen
Marc
M
Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany. jacobsen@mpiib-berlin.mpg.de
Repsilber
Dirk
D
Gutschmidt
Andrea
A
Neher
Albert
A
Feldmann
Knut
K
Mollenkopf
Hans J
HJ
Ziegler
Andreas
A
Kaufmann
Stefan H E
SH
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016133:Polymerase Chain Reaction; D014397:Tuberculosis, Pulmonary / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C105244:RAB33A protein, human; D020691:rab GTP-Binding Proteins