Rat Thymectomy Effects on Leptin Receptor and T-bet: Erythroid Hyperplasia with Maturation Arrest and Suppressed T-Cell-Mediated Hepatotoxicity

Abstract

Thymectomy is an inevitable therapy for thymoma. Therefore, determining hemato-immune changes post-thymectomy is important. Twenty-six normal LEW/Sea rats thymectomized (Tx) at the ages of 38 +/- 5 days were followed without any treatment for 4 months (experiments [Exp] A and B). In addition, 16 LEW/Sea rats Tx at the age of 42 days (Exp C and D) and 10 non-Tx control LEW/Sea rats (Exp E) were immunized with syngeneic male liver cells 2 to 3 times and followed 2.7 months after the first immunization. Flow cytometric (FCM) analysis of mesenteric lymph nodes (MLN) and peripheral blood (PB) showed as follows: among the 26 Tx rats (Exp A and B), MLN lymphocyte population at 4 months postthymectomy was characterized by decreased numbers of CD4+ cells (22%-36%) or alphabeta T-cell receptor (TCR)-positive cells (16%-54%) and increased numbers of interleukin 2 receptors (IL-2R) (>90%). In the 16 Tx-immunized rats (Exp C and D), both alphabeta TCR (MLN) and CD45R (PB) expression on lymphocytes was suppressed with rather high numbers of CD4. Bone marrow (BM) and PB hematological studies of the partially and totally Tx rats indicated the following: 8 BM of the 10 totally Tx males (Exp A) and the 7/10 male spleen showed erythroid hyperplasia with maturation arrest at the stage of basophilic erythroblasts and reticulocytopenia in the PB. One of the 10 males, which had both BM myeloid to erythroid (M/E) ratio of 4.3 and spleen myeopoiesis, was in a more advanced stage, a prestage of pure red cell aplasia (PRCA) with 22% of CD4+ MLN cells. Syngeneic liver cell immunization resulted in the Tx rats as follows: hepatotoxicity based on the immunization was weaker in the 16 Tx rats (Exp C and D) than in the 10 non-Tx rats (Exp E). Polymerase chain reaction (PCR) of PB and MLN showed compensatory activated leptin receptor (LR) and T-bet DNA in 19 Tx rats (Exp A and B) with abnormal FCM findings. The ineffective erythropoiesis at 4 months after thymectomy was explained by the erythroblast LR/erythropoietin receptor (EPOR) dysfunction. The low grade hepatotoxicity in the Tx rats (Exp C and D) was explained by the disturbed Th1 reactions (or the disturbed T-bet gene transcription) at postthymectomy.