A longitudinal study of in vitro IFNgamma production and cytotoxic T cell responses of tuberculosis patients in the gambia.
METHODS
This study was carried out at the MRC Laboratories, The Gambia.


OBJECTIVE
To characterize the antigen-specific IFNgamma production and cytotoxic T cell (CTL) responses of patients during active tuberculosis, treatment, and following recovery.


METHODS
PBMC were isolated from 37 patients with tuberculosis and incubated with either PPD, live M. bovis BCG, or no antigen and IFNgamma production measured after 7 days. CTL activity against these antigens was determined using autologous antigen-pulsed monocyte-derived macrophages as target cells. A subset of these patients (7-18 depending on antigen and assey used) were tested 2 months into drug treatment and 3 months after discharge. A group of blood bank donors (n= 21) were also tested to evaluate IFNgamma responses in endemic controls; a subset (n= 16) were also tested for CTL activity.


RESULTS
The ability to produce IFNgamma in response to mycobacterial antigens correlated with the Mantoux skin test status of the patient. IFNgamma production to live M. bovis BCG was diminished at diagnosis but returned after 2 months of drug treatment, and was sustained after completion of drug therapy. The CTL responses to both PPD and live M. bovis BCG were reduced during the period of drug treatment compared to those at diagnosis, but returned to the original levels after recovery.


CONCLUSIONS
Drug treatment induced marked alterations in the immune responses of tuberculosis patients with induction of IFNgamma production in response to stimulation with live M. bovis BCG. This may indicate activation of both CD4 and CD8 T cells.
Turner
J
J
MRC Laboratories, Fajara, The Gambia.
Corrah
T
T
Sabbally
S
S
Whittle
H
H
Dockrell
H M
HM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012882:Skin Tests; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D007371:Interferon-gamma