CD4+ T cells in lung tissue predict responsiveness to cyclosporin A in interstitial pneumonia

A limited number of case studies have demonstrated the steroid-sparing and disease stabilization effects of cyclosporin A (CsA) combined with corticosteroid in patients with chronic interstitial pneumonia (IP). Although CsA is known to inhibit the proliferation and function of CD4+ T cells, it is not clear what type of IP is responsive to CsA administration.

In order to evaluate whether any lymphocyte subsets in alveolar tissue predict the responsiveness to CsA, morphometric analysis was performed on lung tissue obtained from six IP patients who were treated with a combination of CsA and steroid because the therapeutic effect of steroid alone had been limited.

Cell densities of CD4+ T cells were significantly decreased in the alveolar tissues obtained from CsA responders (n = 3) compared to non-responders (n = 3) (120 +/- 86/mm2 vs 503 +/- 172/mm2, P=0.0495). CD4/CD8 ratios of CsA responders were also significantly lower than those of non-responders (0.315 +/- 0.070 vs 1.975 +/- 0.965, P=0.0463). However, cell densities of CD8+ T cell and areas of B cells aggregates were similar in both groups.

The present observations, contrary to expectation, reveal that lower cell densities of CD4+ T cells and lower CD4/CD8 ratios are associated with responsiveness to CsA in combination therapy, suggesting that pharmacological actions other than suppression of CD4+ T cells explain the efficacy of CsA in patients with chronic IP.