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


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Abstract

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 cellsDesign: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 weeksMethods: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 antigensResults:All of the SHR, regardless of age, possessed arterial antigen-specific CD4+, major histocompatability complex class ll-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-γ 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 ratsConclusions: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

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