Summary.We assessed the role of spinal magnetic resonance imaging (MRI) and bone densitometry as prognostic factors in patients with asymptomatic stage I multiple myeloma (MM) and negative skeletal survey. 55 consecutive patients underwent spinal MRI and 41 of them underwent bone densitometry by dual-energy X-ray absorptiometry (DEXA).Spinal MRI studies showed evidence of bone marrow involvement in 17/55 patients (31%). A diffuse pattern was present in three patients and a focal pattern in 14 patients, nine of them with only one nodular lesion. During a median follow-up of 25 months, 10 patients had disease progression, 8/17 patients with abnormal MRI and 2/38 patients with normal MRI. Median time to disease progression was not reached in both groups but was significantly different for patients with normal and those with abnormal patterns on MRI (P < 0·0001). Lumbar BMD was only slightly decreased compared with normal people (median lumbar Z score ¹ 0·43) and was not of prognostic value. Using a multivariate analysis the only two independent significant prognostic parameters were abnormal MRI (P < 0·001, HR 30·4, 95% CI 4·3-213) and bone marrow plasmacytosis > 20% (P ¼ 0·004, HR 16·4, 95% CI 2·6-104).Thus, spinal MRI but not bone densitometry, appeared to be justified in patients with stage I asymptomatic MM and negative skeletal survey.

NK T cells are an unusual T lymphocyte subset capable of promptly producing several cytokines after stimulation, in particular IL-4, thus suggesting their influence in Th2 lineage commitment. In this study we demonstrate that, according to the cytokines present in the microenvironment, NK T lymphocytes can preferentially produce either IL-4 or IFN-+ . In agreement with our previous reports showing that their IL-4-producing capacity is strikingly dependent on IL-7, CD4 − CD8 − TCR § g + NK T lymphocytes, obtained after expansion with IL-1 plus granulocyte-macrophage colony-stimulating factor, produced almost undetectable amounts of IL-4 or IFN-+ in response to TCR/CD3 cross-linking. However, the capacity of these T cells to produce IFN-+ is strikingly enhanced when IL-12 is added either during their expansion or the anti-CD3 stimulation, while IL-4 secretion is always absent. A similar effect of IL-12 on IFN-+ production was observed when NK T lymphocytes were obtained after expansion with IL-7. It is noteworthy that whatever cytokines are used for their expansion, IL-12 stimulation, in the absence of TCR/CD3 cross-linking, promotes consistent IFN-+ secretion by NK T cells without detectable IL-4 production. Experiments in vivo demonstrated a significant upregulation of the capacity of NK T cells to produce IFN-+ after anti-CD3 mAb injection when mice were previously treated with IL-12. In conclusion, we provide evidence that the functional capacities of NK T cells, which ultimately will determine their physiological roles, are strikingly dependent on the cytokines present in their microenvironment.

Natural killer (NK) T cells are prominent for their prompt IL‐4 and IFN‐γ production upon TCR ligation that enables them to influence acquired immune responses. In the present study we provide evidence that the regulatory functions of this particular T cell subset extend to the myeloid compartment of bone marrow and spleen through its production of hematopoietic growth factors. Bone marrow and spleen NKT cells responded to a single injection of their specific ligand α‐galactosylceramide (α‐GalCer) by producing both IL‐3 and granulocyte‐macrophage colony stimulating factor (GM‐CSF), whose colony‐stimulating activity became detectable in the serum as early as 1 h post treatment. These cytokines were not produced in mice lacking NKT cells (CD1d–/–), whose exclusive involvement in this biological activity was further confirmed by intracellular immuno‐staining. Growth factor production was accompanied by significant changes in the myeloid compartment of treated mice, namely mobilization of myeloid progenitors (colony‐forming unit cells, CFU‐C) and neutrophils from the bone marrow to the periphery. Taken together, our data support the notion that activated NKT cells influence innate immune responses by recruiting myeloid progenitors and granulocytes to the periphery through their production of hematopoietic growth factors.