Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes

A series of experiments was performed to further analyze the effect of age on the induction of SGVHD by separating marrow donors and recipients on the basis of age. The study was designed to assess whether donor and/or host age is a factor that influences the frequency of SGVHD induced with CsA . Lewis rats of either 1, 3, or 6 mo of age were used as donors of bone marrow for lethally irradiated 10-wk-old recipients . The reciprocal experiment was performed in which the 1-, 3-, and 6-mo-old Lewis rats served as recipients of bone marrow from 10-wk-old rats. The recipients were treated with graded doses of CsA for 30 d after irradiation and bone marrow reconstitution . Fig . 2 A illustrates that there was a significant (p < 2 x 10-4) correlation of the age of the marrow donor with the induction of SGVHD in 10-wk-old recipients . The greatest frequency of SGVHD was observed in animals grafted with marrow from rats 1 mo of age. Marrow derived from animals 3 or 6 mo of age resulted in a decreased incidence of SGVHD. Comparatively, the age of recipient also correlated (p < 10-3) with the ability of CsA to induce SGVHD. The youngest recipients had the greatest incidence of SGVHD. The effect of the dose of CsA was more intimately associated with donor age than with recipient age. However, lowering the doses of CsA administered in the recipient study (Fig . 2 B ) was reflected in a less dramatic decline in incidence.