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SUMMARYThe antihuman CD2 MoAb BTI-322 (Lo-CD2a) effectively inhibits T cell responses in vitro to allogeneic cells, which is followed by unresponsiveness to the original stimulator in secondary stimulation. We studied the xenogeneic human antiporcine mixed lymphocyte reaction (MLR), and utilized anti-T cell receptor (TCR) Vβ family antibody-induced cell proliferation to determine the specificity and mechanism. BTI-322 and its humanized version, MEDI-507, effectively inhibited the primary xenogeneic MLR. After suboptimal primary stimulation using lower numbers of xenogeneic stimulator cells, the unresponsiveness in secondary culture was apparent only for xenogeneic stimulator cells of the original SLA haplotype, and not for third-party stimulators or allogeneic cells. The inhibition of primary MLR was not observed for nylon-wool-purified T cells, but was seen after reconstitution of purified T cells with monocytes. Similarly, anti-Vβ family-specific stimulation showed family-specific unresponsiveness in secondary culture. This required the presence of the whole BTI-322 molecule: a F(ab′)2 fragment was not effective. T cells of a distinct Vβ family were depleted after stimulation with an anti-Vβ family-specific antibody and BTI-322. We conclude that the inhibition by BTI-322 of a primary xenogeneic MLR or the response to an anti-TCR Vβ antibody is associated with unresponsiveness upon restimulation, due to activation-associated cell depletion. In this process, the interaction between monocytes and the Fc part of the antibody is involved. This unique characteristic of BTI-322 suggests the potential of the antibody for tolerance induction in vivo, besides the potential use as a T cell depleting agent.

In 153 patients with biopsy-proven primary systemic amyloidosis (AL), serum creatinine level correlated with median survival (creatinine less than or equal to 115 mumol/L [1.3 mg/dL], 2.56 months; creatinine greater than 115 mumol/L [1.3 mg/dL], 14.9 months; P = 0.007). The 24-hour urine total protein excretion was not correlated with survival. Patients who excreted monoclonal lambda light chains in the urine had an inferior survival (12 months) compared with those with kappa (30 months) or no monoclonal protein (35 months) in the urine (P = 0.01). The presence of lambda monoclonal protein was not associated with a higher median creatinine level. A monoclonal protein was detected in the urine in 76% of patients; when patients with more than 1 g of protein in the urine were studied, however, a monoclonal protein was detectable in 86%. The overall kappa-lambda ratio was 1:2.56, but as the urinary protein loss increased, the kappa-lambda ratio shifted to 1:4.7 for those with more than 3 g of protein in the urine.