Suppression of experimental allergic encephalomyelitis by alpha 2-macroglobulin.

Lewis rats sensitized with guinea-pig spinal cord in Freund's complete adjuvant developed an acute-phase protein response. This was characterized by a marked increase in plasma alpha 2-macroglobulin (alpha 2 M) levels which, however, declined towards normal values before the onset of clinical signs of experimental allergic encephalomyelitis (EAE). In contrast, levels of two other acute-phase proteins, fibrinogen and caeruloplasmin, remained variably elevated over the entire study period. Recovery from EAE coincided with an increase in alpha 2 M levels. Infusion of purified alpha 2 M effectively protected the rats against clinical EAE and this was associated with a restimulation of the acute-phase response. The protected rats were shown to be sensitized to myelin basic protein and to have comparable mononuclear infiltration of the central nervous system with the diseased animals. It is postulated that the infusion of alpha 2 M leads to the inhibition of the effector pathways of the delayed type hypersensitivity response.

Inhibition of allergic encephalomyelitis by the iron chelating agent desferrioxamine: differential effect depending on type of sensitizing encephalitogen.

Induction of experimental allergic encephalomyelitis (EAE) in Lewis rats by injection of guinea pig (GP) spinal cord homogenate (SCH) plus adjuvant (SCH-CFA) can be inhibited by treatment with the iron chelating agent desferrioxamine (DFOM). Interestingly, induction of EAE with purified myelin basic protein (BP-CFA) is not inhibited with DFOM. This dichotomy does not appear to be due to any quantitative differences in the two inocula since minimal clinical EAE produced by threshold levels of BP is not inhibited with DFOM. Passive EAE is not inhibited irrespective of the type of encephalitogen used to sensitize the donors. This suggests that the inhibitory effect of DFOM is acting on the afferent limb of the immune response to SCH-CFA. Injection of BP-CFA and SCH-CFA into the same site, mixing BP with central nervous system (CNS) lipids, or incorporating BP into liposomes, all induce EAE which can be partially inhibited by treatment with DFOM. These results support the hypothesis that the close association of lipids with the encephalitogen (i.e. BP) in SCH required extensive lipid breakdown before adequate antigen presentation can occur, and it is at this level that DFOM exerts its inhibitory effect.

Changes in the surface of virus-induced cells recognized by cytotoxic T cells. I. Minimal requirements for lysis of ectromelia-infected P-815 cells.

P-815 mastocytoma cells developed susceptibility to immune T-cell-mediated cytolysis shortly after infection by ectromelia virus. Intracellular viral replication and late protein synthesis seem to bu unnecessary events. Interference with early protein synthesis, however, inhibits the development of susceptibility to lysis. The important intracellular events necessary for subsequent cytolysis appear to occur within 1 hour of infection. Virus rendered non-infectious by ultraviolet irradiation but not by gamma irradiation is able to induce these changes. By determining the minimum and essential events of the infectious process which result in T-cell-mediated cytolysis, the task of establishing the molecular changes occurring in the target cell surface membrane necessary for immune T-cell recognition should be simplified.

Effects of thymus-independent (B) cells and the H-2 gene complex on antiviral function of immune thymus-derived (T) cells.

Antiviral activity in vivo exerted by ectromelia virus-immune spleen cells transferred to ectromelia-infected recipients and cytotoxicity against virus-infected target cells in vitro were both properties of non-immunoglobulin (Ig)-bearing cells (which included T cells). Ig-bearing cells, including thymus-independent (B) cells and antibody-secreting cells, were much less active in vivo when injected alone and tended to block rather than amplify the effect triggered by T cells. Ig-bearing cells were also slightly active in vitro, possibly because some T cells have detectable Ig. Antiviral effects in cell transfer experiments were seen only when immune cell donors and infected recipients shared the same H-2 gene complex. These results are consistent with the hypothesis that the T cell response to ectromelia infection is directed against specific virus-induced change(s) in antigen(s), specified by gene(s) in the H-2 complex, which appear in virus-infected cells.

Cell-medicated cytotoxicity against ectromelia virus-infected target cells. III. Role of the H-2 gene complex.

The role of the H-2 gene complex in expression of cytotoxicity exerted by specific ectromelia-immune thymus-derived (T) cells against ectromelia-infected target cells was examined. A repertoire of inbred mouse strains (some congenic) including the H-2 haplotypes k, d, b, s, q, the recombinant H-2a(k/d) and F1 hybrids (k/b and d/b) were immunized with virus and their spleen cells tested 6 days later, at the peak of the primary response, against H-2k,H-2d and H-2b target cells. Significant specific cytotoxicity occurred only when the immune cell donors and the target cells shared all or part of the same H-2 gene complex. For example, H-2a (k/d) immune cells killed both H-2k and H-2d target cells. There was no detectable effect of the non-H-2 genetic background, H-2 public specificities, or the M-locus. Target cells infected with ectromelia virus exhibited quantitative or qualitative changes (or both) in expression of normal H-2 antigens as indicated by reduced susceptibility to killing by T cells activated against H-2 antigens in mixed lymphocyte culture. These data are consistent with the hypothesis that T cells in this system are responding to virus-induced, specific changes in antigens on infected cells which are controlled by genes in the H-2 complex; these genes seem likely to be those coding for H-2 private specificities, or genes closely linked to them.

Serological assessment of rubella during pregnancy.

In 45 patients with rubella-like illnesses during pregnancy serological tests showed that the clinical diagnosis had been accurate in only 20. Since only 16 of these patients had presented for laboratory investigations within a week of the onset of symptoms, the value of haemagglutination-inhibition tests was considerably reduced; the diagnosis in these cases was confirmed by complement-fixation and rubella-specific IgM tests.Of 172 patients exposed to a rubella-like illness, only 17 were seronegative; 105 sought advice within two weeks of exposure, and therefore the haemagglutination-inhibition antibody tests were useful in determining immunity. Since the clinical diagnosis of rubella was proved incorrect in a number of cases, these pregnancies were saved. Hence both doctors and patients should report both exposure to and rubella-like illnesses as early as possible, so that laboratory investigations may be carried out without delay.