Isolation of T-cell clones with specificity for arterial antigen from spontaneously hypertensive rats.

OBJECTIVE

It has been postulated that hypertension in the spontaneously hypertensive rat (SHR) results from autoimmune damage to the SHR vasculature. The objective of this study was to isolate autoreactive T-cells specific for arterial antigens, and to characterize these cells.

DESIGN

The presence of autoreactive T-cells in the SHR has not been studied previously. Lymphocytes were isolated from spleens obtained from SHR and Wistar-Kyoto (WKY) rats aged 4, 8, 12, 16, 20, 24 and 28 weeks.

METHODS

Limiting dilution analysis was used to clone and to establish arterial antigen-reactive T-cell clones. The specificity of these clones was assessed by measuring lymphokine production and T-cell proliferation induced by arterial antigen and by irrelevant control antigens.

RESULTS

All of the SHR, regardless of age, possessed arterial antigen-specific CD4+, major histocompatability complex class II-restricted T-cells. The responses of freshly isolated spleen cells to arterial antigen were weaker than the proliferative responses of interleukin-2-expanded T-cells to arterial antigen. The T-cell clones also produced interleukin-2, interleukin-4 and interferon-gamma in response to arterial antigen. However, the presence of T-cells specific for arterial antigen is not unique to SHR, since a similar response was seen in normotensive WKY rats.

CONCLUSIONS

The results indicate the existence of T-cells specific for arterial antigen in the spleens of both SHR and WKY rats. Thus, arterial antigen-reactive T-cells cannot be the initial cause of hypertension, but the activation of such autoreactive T-cells might be important in the development of hypertension.