T-CELLS IN HYPERSENSITIVITY PNEUMONITIS - EFFECTS OF INVIVO DEPLETION OF T-CELLS IN A MOUSE MODEL

C57BL/6 mice were given intranasal instillation of optimal doses of the actinomycete Faeni rectivirgula 150-mu-g/mouse 3 days/wk), an important offending agent causing hypersensitivity pneumonitis. This instillation was associated with a very significant increase in the lung weight of the mice and also a large increase (10-fold) in the number of cells recovered from the bronchoalveolar lavage (BAL) of instilled mice. Also, this instillation was associated with a very significant fibrosis at 4 and 8 wk (2-fold increase in hydroxyproline levels in the lungs). We determined the effect of depleting certain T-cell subsets on the progression of this inflammatory disease. Elimination of the L3T4 subset did not significantly affect the increase in the lung index, the lung cellular influx, or its profile. Fibrosis was also unaffected by this depletion of L3T4+ cells. Similarly, depletion of Lyt2+ (CD8+) cells did not lead to significant changes in these disease parameters. Depletion of all T cells (Thy1+) was also ineffective at modifying the number of infiltrating cells and the lung index score. However, identification of cell types in BAL showed that mice depleted of Thyl+ cells had a cellular influx that was almost exclusively neutrophilic throughout the instillation period, whereas control mice developed only a transient neutrophilic response to F. rectivirgula instillation, which was replaced by a recruitment of mononuclear cells, mostly macrophages. Also, depletion of Thyl+ cells before and during F. rectivirgula challenge had no effect on tumor necrosis factor-alpha levels in the BAL of treated mice (63 +/- 13 U/ml in anti-Thyl.2 antibodies treated versus 52 +/- 10 U/ml in the BAL of control mice given F. rectivirgula). The depletion of T cells with anti-Thyl.2 had a biomodal effect on lung fibrosis determined by F. rectivirgula. This depletion of T cells in the lungs delayed the appearance of massive fibrosis, but increased the collagen deposition in the later stages of the disease, when compared with challenged mice treated with control antibodies (P < 0.05). Overall, these results suggest that T cells play a role in the fibrotic process of hypersensitivity pneumonitis, a detrimental one in the early phase but a beneficial one in the later phase.