Analysis of lymphocyte subsets in patients with aplastic anemia before and during immunosuppressive therapy

Abstract

To define the contribution of T-lymphocyte subsets in the development of aplastic anemia (AA), T-cell subpopulations including alpha beta T cells, gamma delta T cells, and delta TCS1-positive gamma delta T cells, were analyzed by cytophotometry in the peripheral blood (PB) and bone marrow (BM) of patients with AA before and after 6 weeks of therapy with anti-lymphocyte globulin (ALG), methylprednisolone, and cyclosporin A (CSA). In nine patients with AA a significant decrease of PB- and BM-derived T cells was observed after 6 weeks of therapy as compared with normal controls. At diagnosis, the CD4/CD8 ratio in PB and BM of the patients did not differ from the ratio in the control population; however, a reversed ratio (< 1) was present in PB as well as in BM after weeks of therapy. Interestingly, lymphocytes expressing the gamma delta T-cell receptor (TCR tau delta) were significantly decreased both before (PB 1.2 +/- 0.1%; BM 0.8 +/- 0.1%) and after 6 weeks of therapy (PB 0.7 +/- 0.1%; BM 0.7 +/- 0.1%) as compared with healthy controls (PB 2.4 +/- 0.2%; BM 2.3 +/- 0.2%). However, the proportion of the gamma delta-T-cell subpopulation expressing the delta TCS1 phenotype was markedly increased before (PB 42 +/- 3.5%; BM 31 +/- 3%) and especially after 42 days of therapy (PB 77 +/- 12%; BM 45 +/- 2%) as compared with that in normal subjects (PB 19 +/- 2%; BM 9.7 +/- 0.8%). At present, follow-up is under evaluation to correlate these findings with hematological response. The pathophysiological significance of the observed alterations within the T-cell subsets and especially the gamma delta T-cell populations will require further functional analyses, in particular since delta TCS1-positive gamma delta T cells exhibit autoimmunological capacity.