Spontaneously hypertensive rat: lymphoid depression is age dependent and mediated via a mononuclear cell subpopulation

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR), particularly in mature animals with established hypertension. The current study examined the time course of development of immune dysfunction and defined its cellular basis in male SHR and control normotensive Wistar-Kyoto rats (WKY). Mitogen-induced proliferative responses in lymphoid cells obtained from induced proliferative responses in lymphoid cells obtained from SHR thymus and spleen before (age 4 wk) and during the development of (ages 8 and 12 wk) hypertension and in age-matched normotensive WKY were monitored. A 50% reduction in concanavalin A (Con A)-induced proliferative responses was seen in SHR thymocytes compared with those of WKY at 12 wk only, suggesting differences in immature T-cell populations. Con A-induced T-cell proliferative responses in splenocytes also differed between strains: greatest (as much as 8-fold) decreases were found in 12-wk-old SHR. Similar findings were obtained in splenocytes stimulated with lipopolysaccharide (LPS), indicating differences in B-cell function. Mononuclear cells depleted of their adherent cell population were prepared from SHR and WKY at 12+ wk of age and assayed for their proliferative responses to LPS and Con A. The remaining nonadherent mononuclear cells of SHR had proliferative responses equal to or greater than those of WKY. Further, when SHR splenic mononuclear cells were allowed to adhere to plastic, and the adherent fraction was co-cultured with either SHR G-10 nonadherent or unfractionated SHR splenic mononuclear cells, proliferative responses were suppressed by as much as 88%.(ABSTRACT TRUNCATED AT 250 WORDS)