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A number of reports have suggested that the spleen plays a key role in the regulation of immunity to malaria but the role, if any, of other tissues is less clear. Furthermore, numerous functional changes occur in the spleen following malaria infection and it is not known whether the spleen's role relates primarily to its content of malaria-specific lymphocytes or to the altered structure and function that has occurred. To address these issues we have generated splenic chimeras by transplanting spleens between Plasmodium berghei-immune and naive rats. In the absence of a functional spleen, specific immune responses from both isolated splenic and non-splenic cells can partially control infection. However, an immune spleen in a naive rat can solidly protect the animal from malaria and a normal spleen in an otherwise immune rat can provide enhanced protection over the non-splenic state. Thus, in the presence of functional splenic architecture both splenic and non-splenic malaria-specific lymphocytes operate more effectively. However, these studies do demonstrate an important role for non-splenic tissue in immunity at least for P. berghei in the rat. The study could have important implications for induction of protective immune responses by vaccination and suggests that malaria-specific lymphocyte responses induced in the periphery following vaccination could interact with parasites in both spleen-dependent and spleen-independent ways.

In this study, we show that cells encoded by donor-type major histocompatibility complex (MHC) class I antigens effectively migrate into the thymus of the host after liver transplantation. However, the thymus is not essential for the induction and maintenance of tolerance after orthotopic rat liver transplantation (OLT). Liver allografted rats in the DA(RT1a) into PVG (RT1c) combination survived without immunosuppressive agents. The thymus of the host showed a transitory atrophy and returned to normal weight 4 weeks after OLT. Donor antigens were detected in the host thymus after OLT. Adult PVG rats that had been thymectomized 1 week before implantation of DA liver grafts showed liver graft survival without immunosuppression. DA heart grafts were heterotopically transplanted into the PVG thymectomized, liver-grafted rats 1-4 weeks after OLT. No rejection of the cardiac allografts was observed. Systemic tolerance was induced and maintained in the absence of the thymus.

An adoptive transfer assay system was used to investigate the ability of serum from tolerant, liver-grafted rats to inactivate normal thoracic duct lymphocytes. PVG rats were rendered tolerant of DA alloantigens by liver grafting. Serum taken from such rats was used to treat normal PVG thoracic duct lymphocytes (TDL) in vitro and the transplant reactivity of the cells then tested in an adoptive transfer assay. Specific decreased responsiveness compared with TDL treated with normal sera was observed, indicating the functional elimination of alloreactive clones by agents in liver-graft serum.

The immunosuppressive activity of serum from PVG rats following orthotopic transplantation of DA liver has been examined in vitro. Liver grafts in this combination are never rejected, but induce a state of specific transplantation tolerance in the recipient. Serum from such tolerant animals was able to inhibit proliferation of normal PVG lymph node cells in response to DA stimulators in the mixed lymphocyte reaction (MLR); inhibition was specific for donor (DA) antigens. Interleukin-2 (IL-2) production during the MLR was also reduced. The production of anti-DA cytotoxic T cells developing in the MLR was not affected, but the total yield of such cells was reduced. Evidence was obtained that part of the inhibitory serum activity was due to IgG antibody against class II RT1a alloantigens. Thus, a purified IgG fraction retained much of the inhibitory activity which could be removed by an anti-IgG absorbent. Studies of MLR inhibition in different rat strains indicated the anti-class II specificity of the inhibitory IgG. Lymph node cells from DA-liver-grafted PVG rats responded normally against DA stimulators in vitro, and this MLR was also blocked by the inhibitory IgG. Our results suggest that anti-class II allo-antibody may play a role in immunosuppression and long-term graft survival following liver transplantation in this combination.

The effect on graft rejection of lymph from rats rendered tolerant of donor antigens by liver transplantation has been studied. Transfer, by daily intravenous injection, of lymph from PVG rats grafted with DA livers prolonged the survival of DA skin, kidney and heart grafts in normal PVG recipients. The effect was specific for the antigens of the liver donor. Suppression was short-term only; thus, after lymph injections were stopped, rejection occurred with a time course approximating a normal first-set reaction. The result suggests a reversible interference by materials in the tolerant lymph with early stages of sensitization of the recipients.

We examined the expression of hybrid phenotype in 236 adults with acute lymphoblastic leukemia (ALL; 188 B-lineage ALL and 48 T-lineage ALL). In B-lineage ALL, myeloid antigen (mAg) CD15 was concentrated in CD10-CD20- cases (49%); CD13 (42%); and CD33 (43%) in CD10+CD20- cases. This trend had no correlation with the presence of Ph1 or t(4;11) chromosomal abnormality. T-cell antigen CD2, CD4, and CD7 was seen in four, four, and two cases, respectively, and CD4+ and CD7+ cases commonly expressed CD13 and/or CD33 (CD13/CD33). In T-lineage ALL, expression of mAg, CD11b (47%), CD13 (38%), CD15 (28%), and CD33 (51%) was restricted to CD3- cases. B-cell antigen CD19 was found in two cases with CD7 solely as T-cell antigen, and these cases possessed CD13/CD33. CD21 was detected in three cases with CD3. In whole ALL, CD13/CD33 was associated closely with the presence of stem-cell antigen CD34, and in T-lineage ALL, CD13/CD33 had a significant correlation with additional stem-cell features, such as HLA-DR, multidrug resistance 1 (MDR1) and c-kit gene expression. Our results suggest that immature ALL cells frequently express B+M+, T+M+, and occasionally B+T+M+ phenotype; that B+T+M- phenotype is extremely rare; and that mAg expression in B-lineage ALL is complicated as compared to T-lineage ALL.