The role of spleen in the pathogeny of aplastic anemia related to increased number of CD3+ CD8+ FcR+ cells.

The role of spleen in the pathogeny of aplastic anemia (A.A.) related to excessive suppression, and the value of splenectomy in the treatment of this disorder is still debated and unclear. In an attempt to find out why some patients respond to surgery and others do not, an immunologic study was carried out in 16 patients with aplastic anemia. Lymphocytes surface markers CD3, CD4, CD8, HLA-DR, Fc receptors (FcR) and CD4/CD8 ratio were determined before and after splenectomy in the patients' peripheral blood, and in the spleen. In addition, the number of granulo-monocytic colony forming cells (GM-CFC) before and after splenectomy was estimated. Nine of the cases showed increased CD3+ CD8+ FcR+ cells, reversed CD4/CD8 ratios (both, in peripheral blood and in spleen), and a low number of GM-CFC. In all these cases, splenectomy induced an improvement of the clinical, hematological, and immunological parameters, thus suggesting that spleen represents an important "reservoir" for CD3+ CD8+ FcR+ cells, which seem to exert a suppressor effect on the hematopoietic progenitors. In splenectomized patients who did not respond to surgery, the pathogenic mechanism was probably related to defective help (3 cases with low values of CD4+ cells), to defective suppression (2 cases with decreased number of CD8+ cells), to a stem cell defect or a deficiency in the stem cell microenvironment (2 cases with normal helper/suppressor ratio). These observations support the conclusion that splenectomy is indicated and may be successful only when the phenotypic markers show an increased number of CD3+ CD8+ FcR+ cells.