Recirculating lymphocytes (RL) 1 are long-lived small lymphocytes which migrate continuously from blood to lymph, predominantly at specialized traffic sites in lymph nodes (LN) (1, 2). In individual LN, recirculation of lymphocytes accounts for over 95% of the cell output (3). In LN undergoing an immune response, where the cell output may increase by as much as 10-fold over the first 48 h after antigen, the migration of RL from blood to lymph still accounts for over 95% of the cell output (3-5).The observation that increased numbers of intravenous (i.v.)-injected ~lCr-labeled lymphocytes are present in LN after antigen stimulation has been attributed to a failure of RL to leave LN, as a direct consequence of antigen priming (6, 7). The transient fall in cell output in the efferent lymph of an antigen-stimulated LN was originally considered by Hall and Morris as possibly reflecting a temporary reduction in the entry of RL into the LN (8). Hall (9) has since reported that lymphocytes are entering a LN from the bloodstream during a period when the output of cells from an antigen-stimulated LN is decreased.Thus, at present, the effect of antigen on the migration of RL through LN is interpreted in two contradictory ways. According to one view, antigen provokes an increase in the input of lymphocytes from the blood into LN but is assumed to prevent those same lymphocytes from leaving the LN (6, 7). According to the other view, antigen provokes both an increased input of lymphocytes from blood into LN and an increased output of the same lymphocytes into the efferent lymph (3-5).Recently, by infusing i.v. ~Cr-labeled autologous RL obtained from efferent lymph draining single lymph nodes, we have demonstrated (10) that the majority of RL required about 30 h to pass from the bloodstream through a single resting LN and reach the efferent lymph. The present experiments were designed to decide between the conflicting opinions on immune response traffic changes and to examine the effects of antigenic stimulation on the migration of RL through single LN. In particular, to determine how the presence of antigen ~Abbreviations used in this paper: BCG, Bacille Calmette-Gu~rin; HRBC, horse red blood cells; i.v
Low‐affinity receptors (Fc epsilon R) and secreted factors (IgE‐BF) which bind to immunoglobulins of the IgE isotype play a key role in the regulation of human IgE synthesis. We report here the cloning of a cDNA coding for the Fc epsilon R of the human B‐lymphoblast cell line RPMI 8866. The nucleotide sequence of this cDNA predicts a polypeptide with 321 amino acids and a mol. wt of 36,281 daltons. A functional Fc epsilon R capable of binding IgE was expressed in Chinese hamster ovary cells after stable transformation with the cDNA which had been cloned into a mammalian expression vector. Amino acid sequence analysis of IgE‐BF purified from RPMI 8866 cells revealed an amino‐terminal sequence of 19 residues which coincides with the predicted amino acid sequence of the Fc epsilon R, starting at residues 148 and 150. A computer search with the translated amino acid sequence of the Fc epsilon R revealed a domain of 120 amino acids having striking homology to the human asialoglycoprotein receptors.
Using cannulated single lymph nodes in sheep the migration of 51 Cr‐labeled autologous and allogeneic recirculating lymphocytes (RL) into efferent lymph was studied after i. v. infusion and infusioninto an afferent lymphatic. The majority of autologous and allogeneic RL appeared in efferent lymph 27–36 h after their infusion i. v. and 6–12 h after intralymphatic infusion. The recovery of i. v. infused allogeneic RL in efferent lymph was only 5–10% that of autologous RL. In contrast, there was no difference in the recovery of autologous and allogeneic RL after infusion into an afferent lymphatic. In primed animals the migration of allogeneic RL through a lymph node was completely inhibited.
Twenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 to 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE) ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (less than or equal to grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8 degrees C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P less than .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, beta 2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1 beta were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.
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