Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema

Background: It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8(+) T lymphocytes, the lasts having increased cytotoxic activity. Because systemic inflammation is also a component of emphysema, we hypothesize that peripheral CD8(+) T lymphocytes of emphysematous smokers who show evidence of systemic inflammation will have higher expression of cytotoxic molecules. Methods: We assessed parameters of systemic inflammation in normal individuals (smokers or non- smokers) and in emphysematous subjects with an active smoking history by measuring serum interleukine- 6, C- reactive protein, and tumor necrosis factor. Expression of perforin, granzyme B, and FasL protein by CD8(+) T lymphocytes, CD4(+) T lymphocytes, and natural killer cells were assessed by flow cytometry while perforin, granzyme B, and FasL mRNA expression were measured on purified systemic CD8(+) T lymphocytes by real-time PCR. Results: Emphysematous smokers had higher levels of serum interleukine- 6 than normal subjects. Even with the presence of systemic inflammation in emphysematous smokers, the percentage of peripheral CD8(+) T lymphocytes, CD4(+) T lymphocytes, and NK cells expressing perforin and granzyme B protein was not different between the three groups. Conclusion: Despite evidence of systemic inflammation, peripheral T lymphocytes of emphysematous smokers did not show higher levels of cytotoxic markers, suggesting that increase of activated T lymphocytes in the emphysematous lung may be due to either activation in the lung or specific peripheral recruitment.