ISOLATION OF T-CELL CLONES WITH SPECIFICITY FOR ARTERIAL ANTIGEN FROMSPONTANEOUSLY HYPERTENSIVE RATS

Objective: It has been postulated that hypertension in the spontaneous ly hypertensive rat (SHR) results from autoimmune damage to the SHR va sculature. The objective of this study was to isolate autoreactive T-c ells specific for arterial antigens, and to characterize these cells. Design: The presence of autoreactive T-cells in the SHR has not been s tudied previously. Lymphocytes were isolated from spleens obtained fro m SHR and Wistar-Kyoto (WKY) rats aged 4, 8, 12,16, 20, 24 and 28 week s. Methods: Limiting dilution analysis was used to clone and to establ ish arterial antigen-reactive T-cell clones. The specificity of these clones was assessed by measuring lymphokine production and T-cell prol iferation induced by arterial antigen and by irrelevant control antige ns. Results: All of the SHR, regardless of age, possessed arterial ant igen-specific CD4(+), major histocompatability complex class II-restri cted T-cells. The responses of freshly isolated spleen cells to arteri al antigen were weaker than the proliferative responses of interleukin -2-expanded T-cells to arterial antigen. The T-cell clones also produc ed interleukin-2, interleukin-4 and interferon-gamma in response to ar terial antigen. However, the presence of T-cells specific for arterial antigen is not unique to SHR, since a similar response was seen in no rmotensive WKY rats. Conclusions: The results indicate the existence o f T-cells specific for arterial antigen in the spleens of both SHR and WKY rats. Thus, arterial antigen-reactive T-cells cannot be the initi al cause of hypertension, but the activation of such autoreactive T-ce lls might be important in the development of hypertension.