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Published on: July 11, 2015
Human in vitro immune responses to Mycobacterium tuberculosis
M L Wilsher1, C Hagan, R Prestidge
1Department of Respiratory Medicine, Green Lane Hospital, Auckland, New Zealand. mwilsher@ahsl.co.nz
Insights
T helper 1 (TH1) cell responses are seen in patients with limited tuberculosis, while severe disease shows T helper 2 (TH2) responses. Both immune responses may be crucial for protection against high bacterial loads.
Area of Science:
- Immunology
- Infectious Diseases
- Cellular Biology
Background:
- T helper cells differentiate into subsets like TH1 and TH2, influencing immune responses.
- Understanding T helper cell responses to mycobacterial antigens is key for tuberculosis (TB) management.
- This study investigates in vitro immune responses to mycobacterial antigens in TB patients.
Discussion:
- Patients with healed or extrapulmonary TB exhibit TH1-like immune responses.
- Severe and disseminated TB cases show TH2-like antibody production alongside high gamma interferon (IFN-γ).
- The interplay between TH1 and TH2 responses is critical for controlling high bacillary loads in TB.
Key Insights:
- In vitro T helper cell responses correlate with clinical TB disease presentation.
- Specific antibody levels (IgA, IgG1, IgG4) differ between limited and severe TB.
- Gamma interferon production is observed across all TB groups, with trends varying by disease extent.
Outlook:
- Further research into the dual role of TH1/TH2 responses in TB pathogenesis.
- Potential for immune response profiling to guide TB treatment strategies.
- Investigating the impact of host genetics on T helper cell differentiation in TB.
Setting:
T helper cells can be divided into 2 subsets on the basis of their cytokine generation. T helper 1 cells secreting gamma interferon and interleukin 2 appear to be more prominent in patients with limited tuberculous disease.
Objective:
The purpose of this study was to evaluate human T helper cell immune responses to mycobacterial antigens in vitro and correlate these with the clinical features of patients with tuberculous infection or disease.
Design:
We studied 51 subjects and 11 controls who were grouped according to disease involvement as follows: 1) Mantoux negative, BCG negative, no disease; 2) Mantoux positive, no disease; 3) localized extrapulmonary; 4) healed pulmonary; 5) active pulmonary; and 6) miliary/disseminated. Peripheral blood mononuclear cells were cultured with PHA, PPD or Tetanus Toxoid, proliferation assessed and the supernatant analysed using an ELISA for IFN gamma. ELISA was also used to measure M. tuberculosis specific antibodies in the serum.
Results:
Mantoux size correlated with PPD proliferation r = 0.5, P = 0.005 and gamma IFN production r = 0.36, P < 0.01. All groups produced abundant gamma IFN although there was a trend toward higher production in groups 3 and 4. M. tuberculosis specific IgA (P = 0.003) and IgG1 (P = 0.002) was higher in groups 5 and 6. Those patients with limited disease (groups 2-4) had significantly lower levels of IgG4 than patients with severe disease (groups 5 & 6) (P < 0.02).
Conclusion:
In conclusion patients with healed or extrapulmonary disease have immune responses in vitro suggestive of a TH1 (cell mediated immune) response, whereas patients with miliary/disseminated disease have antibody production suggestive of a TH2 response, together with high gamma IFN production. Both TH1 and TH2 responses may be necessary for host protection if there is a high bacillary load.
