Isoantiserum-augmented development of lymphocyte-mediated cytotoxicity.Faanes, R; Walker, M; Choi, Y S
doi: 10.1084/jem.144.5.1284pmid: 1086884
Passive administration of anti-P-814 isoantiserum (IS) with P-815 mastocytoma was shown to augment the development of T-lymphocyte-mediated cytotoxicity (LMC). The LMC activity augmented by IS was specific to immunizing tumor cells, but required the simultaneous administration of P-815 tumor cells and anti-P-815 serum, suggesting that the antigen-antibody complex is involved in the development of specific cytotoxic T cells. The serum component responsible for augmented development of LMC activity appeared to be IgM in that the augmenting activity fractionated in the void volume of a G-200 Sephadex column and appears very early after immunization. Our experimental results suggest the development of specific T-cell cytotoxicity can be directly regulated by specific IgM antibodies.
Expression of equivalent clonotypes in BALB/c and A/J mice after immunization with phosphorylcholine.Rudikoff, S; Claflin, J L
doi: 10.1084/jem.144.5.1294pmid: 62819
Analysis of A/J antibody to phosphorylcholine (PC) revealed a striking degree of similarity to PC-binding myeloma proteins of BALB/c origin. By quantitative idiotypic analysis A/J anti-PC antibody was composed to antibodies bearing binding site idiotypic determinants indistinguishable from two different BALB/c myeloma proteins, T15 and M511. Idiotypic determinants of three other PC-binding proteins, W3207, M167, and M603 were not detected. Isoelectric focusing of the light chains verified the presence of antibodies similar to T15 and M511 and indicated the presence of a third antibody whose light chains had a pI identical to that of M603. When the sequence of A/J heavy chains were compared to the heavy chains of T15, M511, and M603, both the framework and first complementarity regions were identical in all cases. Sequences analysis of the light chains through part of the first complementarity region revealed three chains, one similar to each of the myeloma proteins T15, M603, and M167-M511. The latter two sequences differ by only a single amino acid (a single base substitution) in the first 23 residues, suggesting that the two light chains may be very similar if not identical. Thus, BALB/c and A/J mice which differ genetically at multiple loci including the heavy chain allotype complex locus show a remarkable preservation of their anti-PC antibodies. These results indicate that the genes encoding these antibodies are contained in the germ line.
Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection.Gresser, I; Tovey, M G; Bandu, M E; Maury, C; Brouty-Boyé, D
doi: 10.1084/jem.144.5.1305pmid: 186554
The role of interferon in the pathogenesis of encephalomyocarditis (EMC) virus infection was determined by treating mice with potent, partially purified sheep anti-mouse interferon globulin. In control mice, EMC virus was present in low titers in various visceral organs but attained high titers in the brain towards the 4th to 5th day, at which time mice died with signs of central nervous system disease. In mice treated with anti-mouse interferon globulin, virus was present in high titer in visceral organs 24--36 h after viral inoculation and virtually all mice were dead by 45 h. This rapid evolution of EMC virus infection was not observed in mice treated with the globulin fraction prepared from a normal sheep, from a sheep exhibiting a low anti-mouse interferon-neutralizing titer, nor from a sheep having a high titer of antibody to human leukocyte interferon. The experimental results indicated that anti-interferon globulin neutralized the interferon liberated by virus-infected cells, thus permitting extensive virus multiplication in several visceral organs. We conclude that interferon is an important early component of host resistance to this virus infection.
Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses.Gresser, I; Tovey, M G; Maury, C; Bandu, M T
doi: 10.1084/jem.144.5.1316pmid: 186555
The effect of potent sheep anti-mouse interferon globulin was investigated in several different experimental virus diseases of mice. In anti-interferon globulin-treated mice infected intraperitoneally with herpes simplex virus (HSV) type I, the latent period was shortened, and the overall LD50 was increased several hundredfold compared to virus-infected control mice. When HSV was inoculated subcutaneously all anti-interferon globulin-treated mice died, whereas only 5% of virus-infected control mice died. Subsequent treatment with anti-interferon globulin of previously HSV-infected mice did not result in reactivation of HSV. Treatment of adult mice with anti-interferon globulin resulted in an earlier appearance of MSV-induced tumors, a greater number of mice bearing tumors, an increase in tumor size, and an increase in the duration of tumors. All tumors eventually regressed despite reinjection of anti-interferon globulin. Anti-interferon globulin treatment resulted in a rapid onset of disease and death in adult mice inoculated (intranasal) with VSV and in newborn mice infected with NDV. Anti-interferon globulin exerted no effect on the course of influenza virus infection of mice. We conclude that the early production of interferon is an importane element in the response of the mouse to several viruses exhibiting different pathogeneses.
Control of mating preferences in mice by genes in the major histocompatibility complex.Yamazaki, K; Boyse, E A; Miké, V; Thaler, H T; Mathieson, B J; Abbott, J; Boyse, J; Zayas, Z A; Thomas, L
doi: 10.1084/jem.144.5.1324pmid: 1032893
When a male mouse is presented with two H-2 congenic two female in estrus, his choice of a mate is influenced by their H-2 types. The term "strain preference" is used to describe the general tendency of the male population of one inbred strain to prefer two female of one H-2 type rather than another. The term "consistency of choice" is used to describe the added tendency of particular two males of one inbred strain, in sequential mating trials, to prefer two females of the H-2 type they chose in previous trials. Statistical analysis showed trends in the data that support the following conclusions: (a) The choice is made by the male, not the female. (b) The strain preference of two males may favor two females of dissimilar H-2 type (four of six comparisons), or of similar H-2 type (one of six comparisons). (c) Consistency of choice does not always correspond with strain preference. In one of six comparisons of H-2 genotypes there was no strain preference but pronounced consistency of choice by individual two male.This suggests memory, but fortuitous bias is not excluded. (d) Strain preference of the same male population may favor two male of the same or a different H-2 type, depending on which different H-2 type is offered as the choice alternative to self.These findings conform to a provisional model in which olfactory mating preference is governed by two linked genes in the region of H-2, one for the female signal and one for the male receptor. These mating preferences could in natural populations serve the purpose of increasing the representation of particular H-2 haplotypes or of maintaining heterozygosity of genes in the region of H-2.
Connective tissue origin of the amyloid-related protein SAA.Linder, E; Anders, R F; Natvig, J B
doi: 10.1084/jem.144.5.1336pmid: 792382
Protein SAA is a serum protein related to the major constituent of secondary amyloid fibrils, protein AA, and has been suggested to be a precursor of the amyloid protein AA. In the present study, the origin of SAA was investigated by studying human fetal tissues and cultured human fetal fibroblasts with the indirect immunofluorescence technique. Anti-SAA antibodies reacted strongly with cultured fibroblasts producing a fine fibrillary cytoplasmic staining and with extracellular fibrils in loose connective tissues and vessel walls. The reactions were specifically inhibited by absorption with degraded amyloid material, isolated protein AA, isolated protein SAA, and sera from patients with elevated levels of SAA. In contrast, no inhibition was seen with amyloid fibril material devoid of AA protein or by human sera in which SAA was not detectable by double-diffusion tests. These observations showed that SAA-like material is produced by fibroblasts and indicate that it is a normal constituent of developing extracellular connective tissue fibers.
The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen.Naruse, T; Fukasawa, T; Hirokawa, N; Oike, S; Miyakawa, Y
doi: 10.1084/jem.144.5.1347pmid: 993727
The renal tubular epithelial antigen (Tub-Ag) of rats was solublized by Pronase and purified by gel filtration and acrylamide gel electrophoresis. Purified Tub-Ag was a glycoprotein with S20,W value of 8.4. Utilizing radiolabeled Tug-Ag, a sensitive radioimmunoassay for Tub-Ag and homologous antibody (anti-Tub-Ag) was developed. Tub-Ag activity associated with a protein of the same molecular size was demonstrated in the serum, as well as in Pronase extracts of all the organs tested, including kidney, liver, lung, spleen, intestine, stomach, and heart. The physiochemical properties of the Tub-Ag of rats and its distribution were essentially the same as the Tub-Ag of humans, which had been found in immune deposits in the kidney of some patients with idiopathic membranous glomerulonephritis. Rats were immunized with the purified Tub-Ag emulsified in Freund's complete adjuvant and followed for Tub-Ag and anti-Tub-Ag in the serum, as well as for proteinuria and immunohistological changes in the kidney. Serum Tub-Ag dropped sharply after 20 days, when anti-Tub-Ag appeared in the circulation. Persistent, massive proteinuria appeared still later, more than 30 days after injection, when anti-Tub-Ag disappeared and Tub-Ag reappeared in the serum of some of those rats. In others, anti-Tub-Ag in the serum persisted throughout the observation period of 90 days. The pathology of the kidney of the rats with proteinuria was that of a typical membranous glomerulonephritis; thickening of glomerular capillary walls with granular deposits of gamma-globulin and Tub-Ag was observed. On the basis of these results, Tub-Ag in the serum, probably released from cellular membranes of various organs as a physiological metabolite, is considered to maintain the pathological process in the kidney by providing the antigen continuously to form immune complexes.
Correlation of suppressor cell development in parental and F1 hybrid mouse strains with the growth of a parental tumor in vivo.Levy, R B; Waksal, S D; Shearer, G M
doi: 10.1084/jem.144.5.1363pmid: 993728
Parental AKR/J, and AKB6F1 and AKD2F1 hybrid mice were injected subcutaneously with a spontaneously arising AKR/J tumor. The highly responsive AKB6F1 strain never exhibited any depression of immune functioning during the course of tumor growth and regression. The (AKR/J) intermediately responsive strain, while able to generate a successful anti-tumor response, did display a transient reduction of immunological capability, but only during the period tumor growth and not during tumor regression. Cells able to suppress antibody, but not cell-mediated responses, were found. The unresponsive AKD2F1 strain was characterized by both a marked depression of immune responsiveness, as well as the generation of suppressor cells to both antibody, and later, cell-mediated responses. Depression of immune responsiveness, and the generation of suppressor cells, appeared to correlate with the strength or weakness of the anti-tumor response in these strains of mice.