Apparent difference in the roles of spleen and lymph nodes in the pathogenesis of host-versus-graft disease in murine parent/F1 chimeras.

Abstract

Host-versus-graft (HVG) disease is the often fatal immunodeficiency syndrome that can be induced in susceptible strains of mice by the perinatal inoculation of semiallogenic spleen cells. To determine the distribution and engraftment of the donor cells in the spleens and lymph nodes of RFM hosts, sequential tests were done for the presence of (T6 X RFM)F1 cells marked by their ability to form donor-specific antibodies to horseradish peroxidase (HRP) and by the T6 chromosome. Quantitation of cells with intracytoplasmic antibody that bound HRP (HRPBC) and of metaphases with the T6 marker showed that greater than 90% of donor cells were located in the hyperplastic lymph nodes. The pattern of sequential changes in numbers of HRPBC corresponded with the rise and fall in titers of antibodies to HRP. The marked differences in localization of donor cells suggested that host nodes and spleens played different roles. The lymph nodes became the main sources of donor antibodies and the principal repositories of (T6 X RFM)F1 cells capable of replication. The spleen evidently served as a major site of host resistance to engraftment. This was attributed to the ability of host cells there to inhibit selectively the proliferation of the semiallogenic donor cells. It is also proposed that counts of HRPBC measured the vigor of the HVG reaction in host spleen and lymph nodes, because the appearance of virtually all these antibody-forming cells was the result of the maturational effect of the allogenic reaction on F1 donor B memory cells.