Activation of HIV-specific CD8+ T lymphocytes by histamine depends also on the total NK cells

Purpose of the study

The immune dysfunction induced by HIV is characterized not only by depletion of CD4+ T-cells, but also with hypoergy of cytotoxic CD8+ T lymphocytes (CTLs), facilitating the persistence of HIV in the host. We have studied the ability of histamine to stimulate HIV-specific CTLs in HIV+ patients. We evaluated this stimulation in the context of the total number of NK cells.

Methods

Blood samples from 54 HIV-positive subjects were examined. We measured in vitro activation of HIV-specific CTLs (IFN-gamma production) using stimulation by two HIV peptides (gp 120 and gag), histamine, and/or IL-2 and cimetidine by means of ELISPOT assay (BD Bioscience). This activation was compared with total number of NK cells measured using monoclonal antibodies and flow cytometry (BD Facscan). Pair t-test was used for evaluation of the statistical significance.

Summary of results

We found statistically significant differences in activation of HIV-specific CTLs after incubation with peptides compared to peptides + histamine (p = 0.013), peptides + histamine + IL-2 (p = 0.021), and peptides + histamine + cimetidine (p = 0.034). This differences were detected only in patients with levels of NK cells over 0.1 × 10⁹/l (p = 0.05) in comparison with those with level under 0.1 × 10⁹/l (p = 0.18).

Conclusion

HIV-specific CTLs production of IFN-gamma was statistically significantly higher after stimulation by HIV peptides and histamine in HIV-positive subjects compared to the production after stimulation by HIV peptides alone and this production depended also on the number of total NK cells.

Support

Grant of Ministry of Health CR, IGA NR9032-3/2006.