Progress in Rhesus Histocompatibility Typing Resulting from the Second International Nonhuman Primate Histocompatibility Workshop (1973)

The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developd in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.     

Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Lethally irradiated Lewis (LEW) rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period, develop, upon withdrawal of CsA, a graft-versus-host-like disease, so-called CsA-induced autoimmunity (CsA-AI). This T cell-mediated autoimmune disease is thymus-dependent; it is generally held that this disease is a consequence of aberrant T cell recovery brought about by CsA. In this study we determined mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy1.1⁺, TCR αβ⁺) was observed as a consequence of CsA treatment, eventually resulting in decreased absolute peripheral T cell numbers. In these rats no altered CD4:CD8 T cell ratio was observed before onset of CsA-AI; CD4⁺ and CD8⁺ cells consisted predominantly of monocytes (CD4^dim+, TCR αβ⁻) and natural killer cells (CD8⁺, TCR αβ⁻), respectively. LEW rats, x-irradiated, syngeneic bone marrow-reconstituted and treated with CsA, showed a marked and persistent, relative expansion of mature CD45RC⁺, RT6⁻ Th cells. In contrast, Brown-Norway rats treated in a similar fashion, or LEW rats subjected to either CsA treatment or x-irradiation, did not show a comparable expansion of mature CD45RC⁺, RT6⁻ Th cells, nor did these animals develop CsA-AI. The CD45RC⁺, RT6⁻ Th cells produced IL-2, and moreover constituted the only Th subset producing IFN-γ upon stimulation, and therefore were considered as Th1-like effector cells. These results are consistent with the view that a persistent preponderance of Th1 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.     

The Gm-Pi linkage heterogeneity in view of Pi M subtypes

In this study linkage between the loci for Gm (γ-type heavy-chain immunoglobulin markers) and Pi (α₁-antitrypsin/α₁-protease inhibitor) has been shown in families segregating for the Pi M subtypes (Ml, M2, M3 and Msal) as identified by separator isoelectric focusing. The estimate for the Gm-Pi (M-type) recombination is 0-29 (95% limits 0-24-O37) at a peak lod score of 4-31 and with no sex difference. This value is not significantly different from updated recombination frequency estimates for Gm-Pi in Pi MS (0-26) and Pi MZ, SZ and FZ families (0 21). The overall Gm-Pi recombination fraction estimate of 0 26 (95 % limits O23-0-30) at a peak lod score of 20-75 must now be considered as solid. There is a significant heterogeneity within the male Pi MZ families in that the new Finnish families show a higher recombination between Gm and Pi. There is also a possible segregation distortion (Z:M = 23:8). The heterogeneity is discussed in terms of haplotypes, the behaviour of which could be determined by linked genes or chromosomal rearrangements. The possibility that the α₁-antitrypsin level influences recombination frequency has not been ruled out, but cannot explain the heterogeneity within Pi MZ families.     

IgG Humoral Response Against the Antigen 85 Complex Homologues in Leprosy

Antigen 85 complex is the major protein component present in M. bovis BCG culture filtrate (CF). It consists of a family of three proteins: 85A, 85B and 85C. Combining isoelectric focusing and Western blot analysis, we have previously identified different antigenically related proteins present in the CF of other mycobacteria ( M. tuberculosis, M. kansasii, M. avium, M. gordonae, M. fortuitum and M. plilei ) using monoclonal antibodies (MoAbs) directed against the antigen 85 complex of M. bovis BCG.
Humoral immune response directed against these cross-reactive homologues was analysed in sera from 20 patients with multibacillary leprosy (BL/LL), from 20 patients with paucibacillary leprosy (BT/ TT) and from 15 healthy leprosy contacts.
All the antigen 85 homologues identified in the seven CFs by MoAbs were also recognized by IgG present in sera from multibacillary leprosy patients, but not or very faintly in sera from paucibacillary leprosy patients or from healthy subjects.
These results suggest that some of the M. leprae epitopes inducing a significant humoral response in multibacillary leprosy are common to the various 85 antigenically related proteins present in all mycobacterial species.     

Differential effects of sex hormones on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis

In patients with systemic lupus erythematosus, the female-to-male ratio is as high as 10:1. Sex hormones are thought to play a role in this difference in susceptibility. In a previous study, we demonstrated a high susceptibility of female mice to the development of glomerulonephritis after induction of chronic graft-versus-host disease (GVHD), compared with male mice. In order to unravel further this gender-related difference (C57Bl/10*DBA/2)F¹ hybrid mice were either castrated or ovariectomized and treated with 17β-ethinyloestradiol or testosterone-decanoate preceding the induction of chronic GVHD. Testosterone-decanoate reduced significantly the development of albuminuria in females. In contrast, proteinuria of 17β-ethinyloestradiol-treated female mice was in the same range as that of sham-operated mice. Autoantibody levels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17β-ethinyloestradiol-treated female mice than in all other groups. Immunofluorescence studies showed the presence of immunoglobulin and complement deposits in glomeruli of all animals, without significant differences between the experimental groups. Our findings confirm earlier observations, in that testosterone-decanoate is shown to be an inhibitory compound, whereas 17β-ethinyloestradiol has stimulating properties in autoimmunity. Moreover, our results show for the first time differential hormonal effects on autoantibody levels and proteinuria in experimental lupus nephritis.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.