Denian Ba

Natural cytotoxic autoantibody against thymocytes in spontaneously hypertensive rats

Abstract A strain of SHR rats, which spontaneously develops hypertension and periarteritis nodosa, had a decreasing number of rosette-forming T cells in their thymuses and a progressive decline in cellular immune functions by aging. They were found to produce natural thymocytotoxic autoantibody (NTA) detected by a complement-dependent cytotoxicity test. This autoantibody occurred from 1 month of age and throughout life; the incidence was more than 60% of SHR rats at any age. Thymocytes from all six rat strains tested showed similarly high sensitivity to NTA but none of the strains tested produced NTA except the SHR strain. Rosette-forming thymocytes of WKA rats, which were separated by Ficoll gradient, showed much higher cytotoxic sensitivity to NTA than did whole thymocytes and nonrosetting thymocytes. The cytotoxicity of NTA was weak or negative for spleen cells, lymph node cells, bone marrow cells, and blood lymphocytes of WKA rats. However, the cytotoxic activity of NTA was completely absorbed with the thymus, spleen, lymph node cells, and brain homogenates and was partially absorbed with bone marrow cells, but not with liver and kidney homogenates. NTA in SHR rats was an IgM-globulin as determined by sensitivity to 2-ME treatment and by Sephadex G-200 column chromatography. These results suggest that NTA is responsible for the selective suppression of T-cell functions in SHR rats.

The arrest of T cell maturation in spontaneously hypertensive rats with a deficient production of thymic factors.

Spontaneously hypertensive rats (SHR) which regularly develop hypertension and periarteritis nodosa showed a progressive loss of T cell numbers and functions early in life. When six months old and compared with W rats, the original strain of SHR, they were found to possess a reduced number of thymocytes that formed rosettes with guinea pig erythrocytes and that reacted to anti‐Thyl. 1 and anti‐T (W3/13) sera. The number of spleen and lymph node cells which reacted to anti‐T (W3/13) and anti‐helper T (W3/25) sera also decreased. The antibody response of 3‐month‐old SHR spleen cells to SRBC was about one‐fifth that of Wistar rats and progressively declined with age. Subcutaneous grafting of 3‐month‐old SHR thymus tissues failed to promote differentiation and functions of T cells in the spleen of nude mice, whereas 3‐month‐old W thymus tissues showed significant recovery of T cell generation and functions. The T cell functions of old SHR was completely restored by grafting adult W thymus tissues but was not restored by grafting adult SHR thymus tissues. Similar recovery was also obtained by the injection of thymus extracts from W thymus tissues. These results suggest that thymic epithelial cell products regulating T cell maturation may decrease in SHR with increasing age. ACTA PATHOL. JPN. 35 : 351–360, 1985.