Detection of hyperreactive T cells in multiple myeloma by multivalent cross-linking of the CD3/TCR complex

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-independent (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 solubleT11₂ + 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). CO3 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 T11₂ plus T11₃ (P = .01), and PMA plus ionomycin (P = .03) than patients with less than 10% CD8⁺ HLA-DR⁺ cells. Phenotyping of CD45RA (naive) and CD45RO (memory) expressions in resting MM T cells showed a lower ratio of CD45RA to CD45RO in both CD4 (P < .05) and CDS (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.