Disseminated systemic expression of the "local" popliteal lymph node assay in rats.

In contrast to the traditional belief that the popliteal lymph node (PLN) assay of graft-versus-host (GVH) reactivity is a local phenomenon, this study describes significant systemic components of both donor and host lymphoid cell activity. Not only are host radiosensitive lymphocytes of systemic origin necessary for the manifestation of normal PLN hypertrophy, but as few as 2.5 X 10(6) parental lymph node cells (LNCs) injected into the hind footpad of adult F1 hybrid rats disseminate widely, provoking significant systemic GVH reactions, as measured by splenomegaly, and distant lymphadenopathy. Futhermore, locally injected donor LNCs ultimately engender three forms of attenuated GVH reactivity: (1) the dissipation of potentially unlimited GVH reactivity, (2) refractoriness of the host to subsequent rechallenge by GVH-inducing cells, and (3) progressive loss of GVH reactivity in donor LNCs when serially transferred to secondary F1 recipients. Whether this modulation of the cell-mediated immune response is the expression of an anti-recognition structure response by the host or the activation of some other immunoregulatory protein, it is absent or reduced in splenectomized recipients. The data suggest that the spleen provides an immunoregulatory microenvironment in which cell-mediated immune responses, such as the GVH reaction, are modulated.