Decreased expression of CD3zeta and nuclear transcription factor kappa B in patients with pulmonary tuberculosis: potential mechanisms and reversibility with treatment.
BACKGROUND
The protective immune response against Mycobacterium tuberculosis relies both on antigen-presenting cells and on T lymphocytes. In patients with different forms of tuberculosis, varying degrees of T cell function--ranging from positive delayed-type hypersensitivity, in asymptomatic infected healthy individuals, to the absence of the response, in patients with miliary or pulmonary tuberculosis (PTB)--have been reported. The decreased expression of CD3zeta reported in T cells from patients with either cancer or leprosy has provided possible explanations for the altered immune response observed in these diseases.


METHODS
The present study aimed to compare the expression of CD3zeta , nuclear transcription factor- kappa B (NF- kappa B), arginase activity, and cytokine production in 20 patients with PTB, in 20 tuberculin-positive asymptomatic subjects, and in 14 tuberculin-negative control subjects.


RESULTS
Compared with those in tuberculin (purified protein derivative)-negative control subjects, peripheral-blood T lymphocytes from patients with active PTB had significantly (P < .001) decreased expression of CD3zeta and absence of the p65/p50 heterodimer of NF- kappa B. These alterations were reversed only in patients who responded to treatment. Also reported here for the first time is that the presence of arginase activity in peripheral-blood mononuclear-cell lysates of patients with PTB parallels high production of interleukin-10.


CONCLUSIONS
The presence of arginase could, in part, explain the decreased expression of CD3zeta . These findings provide a novel mechanism that may explain the T cell dysfunction observed in patients with PTB.
Zea
Arnold H
AH
Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. azea@lsuhsc.edu
Culotta
Kirk S
KS
Ali
Juzar
J
Mason
Carol
C
Park
Hae-Joon
HJ
Zabaleta
Jovanny
J
Garcia
Luis F
LF
Ochoa
Augusto C
AC
D000328:Adult; D000368:Aged; D001119:Arginase / Q000032:analysis; D017252:CD3 Complex / Q000096:biosynthesis*; D016207:Cytokines / Q000032:analysis; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D006968:Hypersensitivity, Delayed; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016328:NF-kappa B / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic; D013601:T-Lymphocytes / Q000737:chemistry; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D001119:Arginase