The adaptor molecule SAP is expressed in T lymphocytes and natural killer (NK) cells, where it regulates cytokine production and cytotoxicity. Here, we show that SAP, encoded by the SH2D1A gene locus, also has a crucial role during the development of NKT cells, a lymphocyte subset with immunoregulatory functions in response to infection, cancer and autoimmune disease. Following stimulation with the NKT cell-specific agonist alpha-galactosyl ceramide (alphaGC), Sh2d1a-/- splenocytes did not produce cytokines or activate other lymphoid lineages in an NKT cell-dependent manner. While evaluating the abnormalities in alphaGC-induced immune responses, we observed that Sh2d1a-/- animals lacked NKT cells in the thymus and peripheral organs. The defect in NKT cell ontogeny was hematopoietic cell autonomous and could be rescued by reconstitution of SAP expression within Sh2d1a-/- bone marrow cells. Seventeen individuals with X-linked lymphoproliferative disease (XLP), who harbored germline mutations in SH2D1A, also lacked NKT cells. Furthermore, a female XLP carrier showed completely skewed X chromosome inactivation within NKT cells, but not T or B cells. Thus, SAP is a crucial regulator of NKT cell ontogeny in humans and in mice. The absence of NKT cells may contribute to the phenotypes of SAP deficiency, including abnormal antiviral and antitumor immunity and hypogammaglobulinemia.

When allocating resources, people often diversify across categories even when those categories are arbitrary, such that allocations differ when identical sets of options are partitioned differently ("partition dependence"). The first goal of the present work (Experiment 1) was to replicate an experiment by Fox and colleagues in which graduate students exhibited partition dependence when asked how university financial aid should be allocated across arbitrarily partitioned income brackets. Our sample consisted of community members at a liberal arts college where financial aid practices have been recent topics of debate. Because stronger intrinsic preferences can reduce partition dependence, these participants might display little partition dependence with financial aid allocations. Alternatively, a demonstration of strong partition dependence in this population would emphasize the robustness of the effect. The second goal was to extend a "high transparency" modification to the present task context (Experiment 2) in which participants were shown both possible income partitions and randomly assigned themselves to one, to determine whether partition dependence in this paradigm would be reduced by revealing the study design (and the arbitrariness of income categories). Participants demonstrated clear partition dependence in both experiments. Results demonstrate the robustness of partition dependence in this context.

The adaptor molecule SAP is expressed in T and natural killer (NK) cells, where it regulates cytokine production and cytotoxicity. Here we demonstrate that SAP also plays a critical role during NKT cell development. Sap−/− mice lack thymic and peripheral NKT cells and fail to produce cytokines in response to the NKT cell stimulus alpha-galactosyl ceramide. Infection of Sap−/− bone marrow cells with retroviruses expressing wild-type SAP permits NKT cell development after transfer into irradiated recipients. X-linked lymphoproliferative disease (XLP) patients, who harbor germline mutations in the gene encoding SAP, also lack NKT cells. Furthermore, a female XLP carrier demonstrates completely skewed X chromosome inactivation within peripheral blood NKT cells, but not T or B cells. Thus, SAP is a critical regulator of NKT cell ontogeny in humans and in mice. The absence of this cell lineage may contribute to the phenotypes of XLP, including abnormal anti-viral and anti-tumor immunity and hypogammaglobulinemia.