Comparative evaluation of cytokines, T-cell apoptosis, and costimulatory molecule expression in tuberculous and nontuberculous pleurisy.
In this study, we compared several immune parameters in tuberculosis (TB) and nontuberculosis (NTB) pleurisy to gain an understanding of the mechanism behind enhanced Th1 apoptosis that occurs at sites of active Myobacterium tuberculosis (M. tuberculosis) infection. An initial evaluation of the accumulated cytokines in pleural fluid (PF) demonstrated that both TB and NTB pleurisy were associated with prointflammatory cytokines, while only TB pleurisy had augmented expression of interferon (IFN)-gamma and soluble Fas ligand (sFASL). Despite enhanced expression of the apoptosis-inducing molecule in TB pleurisy, T cells derived from both types of pleurisy exhibited significant apoptosis. In both groups, T-cell apoptosis correlated with low expression of CD80 on PF-derived macrophages and elevated accumulation of TGF-beta in the PF. A causative correlation between TGF-beta and low CD80 expression in the two groups was established by in vitro studies demonstrating TGF-beta inhibition of CD80 upregulation in a macrophage cell line. Together, the findings allude to the possibility that activation in the absence of appropriate CD80 costimulation is the mechanism that leads to T-cell apoptosis at sites of active M. tuberculosis infection. Furthermore, the findings also indicate that T-cell apoptosis is perhaps a host regulatory mechanism to limit inflammation, rather than a pathogen-induced immune deviation.
Rajavelu
Priya
P
Department of Immunology, Tuberculosis Research Centre (ICMR), Chennai, India.
Pokkali
Supriya
S
P
Umashankar
U
Bhatt
Kamlesh
K
Narayanan
P R
PR
Salgame
Padmini
P
Das
Sulochana D
SD
D000328:Adult; D000368:Aged; D017209:Apoptosis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010998:Pleurisy / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014396:Tuberculosis, Pleural / Q000276:immunology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D016212:Transforming Growth Factor beta