Adoptive transfer of immunodiabetes in guinea pig; electron microscopy.
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(SJL X BALB)F1 suppressed mice have, in their lymphoid tissues, a population of suppressor T cells directed specifically against a paternal gamma G2a allotype (Ig-1b). Spleen or lymph node cells from these mice were injected into syngeneic nude mice and the effect on thymus-independent synthesis of Ig-1b in the athymic recipients was determined. After the injection of suppressor cells, Ig-1b disappeared from the serum of the recipients in a time course similar to that seen in normal mice. These results indicate that suppression occurs in the absence of thymus-derived helper cells, and they suggest that Ig-1b-producing B cells are the target of allotype-suppressor cells.
Transfer of primary or secondary influenza-immune spleen cells to mice infected intranasally with influenza virus resulted in a significant clearance of virus from the lungs and the protection of the recipients from death. The antiviral activity was associated only with intact, viable cells and was not due to carryover of virus. The effector cell population responsible for the antiviral effect was shown to be T cells. Thus, the removal of adherent, phagocytic and Ig+ cells did not affect the antiviral activity, whereas it was destroyed with antitheta serum and complement. Antiviral activity was specific and was best expressed if the virus used to infect the recipients and to generate immune cells was the same strain. Further work will be necessary to define rigorously the role of different viral antigens in cell-mediated immune response to influenza virus infection.
Histopathology typical of allergic orchitis developed in testes of inbred guinea pigs 16 months after vasoligation. A similar histopathology was found in unoperated testes after unilateral vasoligation. Peritoneal exudate cells from vasoligated guinea pigs transferred identical lesions to syngeneic recipients. The testicular lesions in long-term vasoligated guinea pigs have an immunological basis.
When nonimmune guinea pigs are inoculated intradermally (i.d.) with Rickettsia mooseri (R. typhi), the rickettsiae replicate at the site of inoculation, leading to the development of a grossly observable lesion. In contrast, guinea pigs which have recovered from R. mooseri infection are resistant to challenge and prevent both rickettsial growth and the formation of lesions. To study the mechanisms of this immunity, sera or splenic cells collected from nonimmune or immune guinea pigs were inoculated separetely into nonimmune recipients. Splenic cells collected from immune donors protected R. mooseri-naive recipients from i.d. challenge as measured by control of rickettsial growth and by prevention of development of lesions at i.d. sites of inoculation. In contrast, serum from immune and nonimmune doners failed to protect nonimmune recipients by either criterion.
Female C57BL/6J mice were infected with Trypanosoma cruzi and subsequently given macrophages or lymphocytes from syngeneic donors which had recovered from the acute infection. Mice which received immune peritoneal macrophages, splenic lymphocytes, or lymph node lymphocytes developed lower mean parasitemias and cumulative mortalities than did recipients of nonimmune cells. Neither peritoneal lymphocytes nor splenic macrophages were protective, however. These studies indicate that splenic and lymph node lymphocytes are effective in transferring protection against T. cruzi, whereas the macrophage is somewhat less effective.
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It was revealed that the administration of the spleen cells (SC) of syngeneic animals immunized with a high dose of sheep red blood cells (SRBC) to intact mice led to a marked specific suppression of the recipients' immune response. The donors' SC obtained on the 14th day after the intraperitoneal injection of SRBC had the greatest suppressive activity. The SC of intact animals and mice given rat erythrocytes preliminarily failed to influence the immune response of the intact recipients in their SRBC immunization. Treatment of immune SC with the anti-T-serum (ATS) or the anti-B-globulin (ABG) and the complement considerably decreased or completely eliminated the suppressive activity. Administration of a mixture of two immune SC suspensions one of which was ATS- and another ABC-treated did not produce any suppression of the immune response in the intact recipients. It is supposed that the suppressor cells in the given model were T-lymphocytes expressing the antigens, common of cross-reacting with the B-cells.
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After onset of experimental allergic encephalomyelitis (EAE), guinea pigs can be effectively treated by injection with myelin basic protein (BP). In order to localize the site of action of BP, cells from sensitized donors treated with BP one, two, three, or four times after disease onset have been transferred to normal recipients. One injection of BP has no effect on ability of cells to transfer EAE. Two injections partially inhibit transfer. After the third and fourth injections the sensitized cells lose their capacity to transfer EAE. The therapeutic effect of BP previously demonstrated in actively sensitized guinea pigs must involve the specifically sensitized cells rather than the target organ.
Passive transfer of immune serum alone did not confer protection to recipient mice irrespective of the routes of serum transfer or cercarial challenge of Schistosoma mansoni. Mice that received both sensitized cells and immune serum were protected against challenge by subcutaneous injection of cercariae but not by percutaneous exposure. The immune serum could be transferred as late as 8 days after subcutaneous challenge, suggesting that the protection was afforded in part by a late parasite killing mechanism which functions after the schistosomula have migrated through the lungs.
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Immune suppression (immunoprotection) in experimental autoimmune encephalomyelitis (EAE) was studied in (SJL X BALB/c)F1 mice using inocular of mouse spinal cord homogenate (MSCH), or mouse basic protein of myelin (M-BPM), in Freund's incomplete adjuvant (FIA). Such immunization specifically recruited lymphoid cells which markedly suppressed the capacity of effector lymph node cells from appropriately immunized syngeneic mice to transfer adoptively EAE. Suppression was demonstrable with transfer of bone marrow and spleen cells, but not with lymph nodes or thymus cells. Adoptively transferred suppression was maximal when cells were injected 9-30 days after the suppressive injection. Inhibition of EAE by suppressor cells was specific for the relavant antigen BPM, and required viable cells. Treatment of cells with anti-Thy-1 serum before transfer abolished their suppressor activity. After adoptive transfer of suppressor cells into syngeneic recipients subsequently immunized for EAE, there was inhibition of EAE and reduced cell-mediated immune response to BPM as judged by macrophage migration inhibition assays. Hence, in mice at least, immuno-protection against EAE is explicable by recruitment of suppressor T lymphocytes with the dual capacities of inhibiting development of effector T cells after antigenic stimulation, and of blocking their damaging effects on the antigen in the central nervous system.