Kinetics and specificity of T and B cell responses in relapsing experimental allergic encephalomyelitis

T and B cell responses to myelin basic protein (MBP) and its relevant peptide fragments were examined throughout the course of MBP-induced relapsing experimental allergic encephalomyelitis (REAE) in (SJL X PL)F1 mice. T cell reactivity, measured by the antigen-driven proliferation of lymph node T cells in vitro, was directed predominantly against the encephalitogenic MBP-P2 peptide (amino acids 1 to 37) at all stages of disease. Levels of responsiveness did not correlate with disease expression, but declined over time to a relapse level that was four- to sixfold lower than that observed during peak acute stage reactivity. Relapse responses were further distinguished by the detection of host I-E restrictions on Lyt-1+ T cell recognition of P2, P2 recognition by acute-stage T cells occurring solely in the context of host I-A molecules. These data imply an increase in the heterogeneity of relapse T cell responses to MBP to include clones restricted by additional class II glycoproteins. A role for additional CNS autoantigens in the stimulation of relapse T cells is also considered. Serum antibody responses to MBP or the P2 fragment fluctuated randomly throughout R-EAE when total antibody activity (IgM plus IgG) was measured. However, analysis of individual isotypes of IgG immunoglobulins revealed an apparent correlation between peak antigen-binding activity and disease expression which may reflect either an effector or regulatory role for humoral immunity in recurrent EAE. Patterns of early antibody reactivity also distinguished F1 mice that developed or failed to develop disease signs after immunization, the latter exhibiting a consistent drop in antigen-binding activity 4 to 5 days before the usual onset of acute-stage paralysis. The results are considered with regard to possible mechanisms of chronic disease regulation in an environment of functional T cell suppression.     

Modulation of experimental allergic encephalomyelitis with anti-T suppressor factor antibodies

mAb reactive with T suppressor factors (TsF) were used to alter the course of myelin basic protein-induced experimental allergic encephalomyelitis in (SJL/J x PL/J)F1 mice. In vivo administration of mAb 14-12, reactive with effector TsF, exacerbated the clinical expression of encephalomyelitis as evidenced by prolonged periods of total limb paralysis in affected animals. This aggravation of disease signs is probably related to the inhibition of effector Ts function by mAb 14-12 thus allowing T cell autoreactivity to proceed unchecked. Disease course was influenced more favorably by i.v. administration of mAb 14-30 reactive with a subset of inducer TsF. Ten days of treatment with this mAb resulted in a reduction in the incidence and severity of disease, noted as the development of minimal limb weakness but no paralysis in the majority of affected animals. Adoptive transfer experiments revealed the presence of Ag-specific Ts in mAb 14-30-treated mice that inhibited recipient Lyt-1+ responses to myelin basic protein, the immunizing autoantigen. Suppression by transferred Ts was revealed only by treatment of the donor population with anti-Lyt-1.2 plus C, however, indicating a role for contrasuppressor activity in the regulation of autoimmune T cell function. Results are considered relevant to the potential for immunotherapeutic management of multiple sclerosis in man.     

Growth-regulator Interactions in the Growth of the Shoot System of Avena sativa Seedlings: I. THE GROWTH OF THE FIRST INTERNODE

1. Segments, 3.5 mm. long, cut from the first internode of Avenasativa seedlings grown in complete darkness respond to bothauxins and gibberellic acid by accelerated extension. 2. The optimum concentration of indole-3-acetic acid (IAA) is10 p.p.m. and of gibberellic acid (GA) is 0.1 p.p.m. 3. The degree of stimulation relative to the growth of controlsegments is affected by the inclusion in the segement of thenode between the internode and coleoptile. Thus the gibberellineffect is greatly increased while the IAA effect is decreased.The optimal concentrations are not affected by inclusion ofthe node. 4. These results can best be explained in terms of the supplyby the node tissue of an endogenous auxin which is necessaryfor the expression of GA action. 5. Numerous factorial experiments demonstrated that there isno detectable interaction between applied IAA and GA in thepromotion of first-internode extension. This implies that thepostulated endogenous auxin which synergized GAA action in (4)is either an active form of IAA produced only in the node tissueor is a completely different auxin. 6. No synergism of growth-promotive action can be detected betweenGA and the two synthetic auxins I-naphthylacetic acid and 2,4-dichlorophenoxyaceticacid. 7. p-chlorophenoxy-iso-butyric acid (PCIB) anc 2,4,6-trichlorophenoxyaceticacid (2,4,6-T) act as weak auxins and thus antagonize competitivelythe promotive action of GA. 8. The anti-auxin -(I-naphythyl-methyl-sulphide)propionic acid(NMSP) antagonizes competitively the promotive action of bothIAA and GA. 9. The facts under (5)–(8) suggest that auxins and GAare acting at the same growth-promotion centres and may competefor them. 10. Growth inhibitions are induced by high concentrations ofPCIB, 2,4,6-T and NMSP. The inhibitions produced by PCIB and2,4,6-T are both synergized by supra-optimal concentrationsof IAA while that of NMSP is synergized by supra-optimal concentrationsof both IAA and GA. This similarity of the effects of IAA andGA suggests that their inhibition actions also are of a closelysimilar nature.     

Cytidine Analogues and Stomatogenic Recovery in Amicronucleate Paramecium tetraurelia and Paramecium jenningsi

Removal of the micronuclei of Paramecium tetraurelia and Paramecium jenningsi by micropipetting generates amicronucleate cell lines. These cell lines go through a period of growth depression for several dozen fissions, but they gradually recover. Amicronucleate cells in the depression period characteristically exhibit abnormal oral development, particularly reduction in the length of the buccal cavity and an abnormal pattern of the oral membranelles. To test the notion that the macronucleus is involved in the recovery of amicronucleate cell lines, DNA demethylation drugs were administered to amicronucleates in the depression period. After at least 4 fissions, the treated amicronucleates were assessed for their progress in recovery by scoring the proportion of cells with normal oral membranelles. Cvtidine analogues which demethylate cytosine specifically at the 5 position, namely 5-azacytidine, 5-aza-2'- deoxycytidine and 5-fluoro-2'-deoxycytidine. promoted recovery of the amicronucleates. Cytidine, 6-azacytidine, 2'-fluoro-2'-deoxy-cytidine and cytosine-β-D-arabinofuranoside did not. These results suggest that (i) 5-methylcytosine is present in the macronucleus of these Paramecium species, probably in small amounts and (ii) recovery of amicronucleates involves demethylation of macronuclear DNA. This implies that in normal cells the micronuclei are involved in maintaining the macronuclear DNA in a methylated state and hence the inactivation of the macronuclear sequences that are to be employed for stomatogenic recovery. A general mechanism for the control of gene expression may therefore be employed for the regulation of specific sequences.     

An Ultrastructural Investigation of 180°-Rotated Ciliary Meridians in Tetrahymena pyriformis*

SYNOPSIS. An ultrastructural investigation has been carried out on 180°-rotated ciliary meridians (inverted meridians) in Tetrahymena pyriformis temperature-sensitive mutant (mol^b/mol^b), syngen 1, strain B. The longitudinal, transverse and postciliary microtubular bands, the kinetodesmal fiber, and the parasomal sac, are shown to be disposed at a 180° angle to their normal positions or orientations. Other abnormalities are as folows: the first 2 basal bodies of the inverted meridian fail to organize into “couplets” and the inverted meridian intrudes into the anterior pole region; an extra longitudinal microtubular band is found in one of the cell lines.     

Commitment to the First Cortical Reorganization During Conjugation in Stylonychia mytilus: An Argument for Homology with Cortical Development During Binary Fission

The asexual nature of the first cortical reorganization of conjugation in Stylonychia was analyzed by comparing the effect of amputation performed at different stages of early conjugation to that performed on vegetative cells at different stages of the cell cycle. Amputation of vegetative cells delineated a point of commitment to binary fission at 0.51–0.57 of the cell cycle. Cells amputated before this point were induced to undergo the regenerative mode of asexual development, but those amputated after this point continued with binary fission. In parallel, during conjugation a similar commitment was made around the time of formation of tight mating-pairs: early conjugants amputated around this time might undergo regeneration, and those operated on after this stage continued with the first cortical reorganization as in typical conjugants. The two mates of a pair might differ in their response to amputation, suggesting that the timing of commitment to the first cortical reorganization is not related to the events of conjugation, but rather is individually determined in the vegetative cycle of the cells before they pair up in mating. These observations provide support for the notion that the first cortical reorganization of conjugants is homologous to the asexual mode of cortical development in dividers, according to the theory of developmental heterochrony in the sexual reproduction of hypotrichs. The timing of commitment to the first cortical reorganization was found to temporally correlate with the entrance of the micronuclei into meiosis. Since the first cortical reorganization can proceed without the micronucleus, this raises the possibility that initiation of micronuclear meiosis is closely coupled with, and may be determined by, the commitment to the first cortical reorganization.     

Morphological studies of Asian rice and its related wild species and the recognition of a new Australian taxon

In order to clarify the taxonomy and the interrelationships among Asiatic cultivated rice, Oryza sativa , and its related wild species ( O. rufipogon, O. nivara and O . barthii ), 41 morphological characters were examined. Numerical taxonomic methods were used to analyse the data and to illustrate species relationships.
Distinctive differences among the materials studied suggest the retention of O. rufipogoon, O. nivara and O . sativa as three distinct species. The origin of O. sativa from O. nivara through domestication is discussed. An annual wild taxon from Australia, which had been classified as a form of O. nivara , is shown to be distinct from typical O. nivnra and is raised to specific rank. This species has been named O. meridionalis Ng.