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Ecto-5'nucleotidase (5'NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (Ll%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5'NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5'NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher Ll% than MGUS patients. There was a linear regression of 5'NT on Ll% which was statistically significant: the higher the Ll%, the lower the 5'NT. Because the Ll% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5'NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5'NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5'NT on the Ll%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5'NT deficiency of unseparated T lymphocytes.

The phenotypic pattern of peripheral blood T (PBT) lymphocytes was correlated with diagnosis and clinical status in 63 patients with monoclonal gammopathies (MGs). The numbers of lymphocytes expressing activation and CD11 determinants were significantly increased in suppressor/ cytotoxic and helper/inducer subpopulations of patients with multiple myeloma (MM) and MG of undetermined significance (MGUS). The number of activated suppressor/ cytotoxic cells was closely correlated with diagnosis and disease status. These cells were significantly higher in MM at diagnosis (160 ± 88) than MGUS patients (61 ± 79; P < .01). Their number decreased to MGUS levels in MM in stable remission (58 ± 53), but not in MM with tumor progression (172 ± 102; P < .001). In individual patients, part of these cells specifically adhered to dishes precoated with the related M-protein. No monoclonal T-beta gene rearrangement was detected in PBT and cytotoxic/ suppressor subpopulations from two patients with a large proportion of activated cells.1988 by Grune & Stratton, Inc.0006-4971/88/7203-0044$3.00/0

Cellular immunity was investigated in 43 patients with multiple myeloma (MM) by assessing 3HTdR uptake induced by monocyte-dependent [CD3 monoclonal antibodies (MoAbs), phytohemagglutinin (PHA)] and monocyte-indepen-dent (CD2 MoAbs, ionomycin + phorbolester) stimulations. The former were evaluated in peripheral blood mononuclear cells (PBMNC) and purified T cells; the latter were evaluated in purified T-cell preparations only. MM showed significantly lower PBMNC responses to PHA (P< .001), soluble OKT3 (CD3) (P= .01), and immobilized OKT3 MoAbs (P= .01). On purification of T cells, MM responses were still defective to soluble T112+ T113(CD2) MoAbs (P= .004), phorbol myristate acetate (PMA) plus ionomycin (P <.001), but significantly higher to plastic-immobilized OKT3 (P= .004). In some MM, 3HTdR uptake, interleukin-2 (IL-2) receptor (CD25) expression, and IL-2 production were as high on stimulation with plastic-immobilized OKT3 as that observed in normal subjects under optimal conditions (ie, plastic-immobilized OKT3 plus accessory signals). CD3 hyperreactivity correlated with the number of CD8+HLA-DR+ cells in MM T-cell preparations. MM patients with more than 10% CD8+HLA-DR+cells had significantly higher responses to immobilized OKT3 (P <.001), but lower responses to T112plus T113(P= .01), and PMA plus ionomycin (P =.03) than patients with less than 10% CD8+HLA-DR+cells. Phenotyping of CD45RA (naive) and CD45R0 (memory) expressions in resting MM T cells showed a lower ratio of CD45RA to CD45R0 in both CD4 (P <.05) and CD8 (P< .001) subpopulations. These data indicate that (a) some MM T cells require significantly fewer accessory signals (if any) to express the IL-2 receptor fully, secrete IL-2, and proliferate on multivalent cross-linking of the CD3/TCR complex; and (b) this peculiar state of activation is associated with high HLA-DR expression in CD8+lymphocytes.