CD4+ T lymphocyte depletion attenuates lipopolysaccharide-induced tumor necrosis factor secretion by alveolar...

Mechanisms underlying the control of cytokine secretion by alveolar macrophages are not fully understood. We hypothesized that T lymphocytes or their products modulate the capacity of alveolar macrophages to release cytokines in response to an exogenous stimulus. In this study, we investigated the role of lymphocytes expressing surface CD4 (CD4+) antigen in the regulation of tumor necrosis factor alpha (TNF-alpha) secretion by alveolar macrophages. Specific pathogen-free male BALB/c mice were injected intraperitoneally with 0.3 mg monoclonal anti-CD4 antibody or phosphate-buffered saline. Depletion of CD4+ splenic lymphocytes was confirmed 6 days later by flow cytometry. On day 6, mice were challenged intratracheally with E. coli lipopolysaccharide (LPS, 1-100 micrograms/100 g BW) or phosphate-buffered saline. The lungs were lavaged 3 h later and the bronchoalveolar lavage fluid assessed for TNF activity and cell recovery (total and differential). No TNF was detected in the lavage fluid of animals pretreated with antibody or phosphate-buffered saline and given phosphate-buffered saline intratracheally. However, the saline-treated mice challenged with LPS (100 micrograms/100 g BW) released 3.76 +/- 0.18 ng TNF/ml bronchoalveolar lavage fluid. In contrast, mice depleted of CD4+ T lymphocytes released almost 50% less TNF (1.94 +/- 0.23 ng TNF/ml lavage fluid, p < 0.001) in response to the same dose of LPS.(ABSTRACT TRUNCATED AT 250 WORDS)