Mechanisms of trypanosome-mediated suppression of humoral immunity in mice

Albright, Julia W.; Albright, Joseph F.; Dusanic, Donald G.

doi:10.1073/pnas.75.8.3923

Cited by 25 publications

(11 citation statements)

References 24 publications

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“…A number of viruses (54–57) and other pathogens (58–61) cause suppression of antibody responses during infection. The degree and duration of suppression varies between pathogens and a number of mechanisms have been suggested, ranging from B cell intrinsic effects (56, 59) to suppressor T cells (58) and myeloid cells (60). A common denominator for all these pathogens is that they cause polyclonal B cell activation and that suppression seems to coincide with the polyclonal activation (56–58).…”

Section: Discussionmentioning

confidence: 99%

Retention of Anergy and Inhibition of Antibody Responses during Acute Gammaherpesvirus 68 Infection

Getahun

Smith

Kogut

et al. 2012

The Journal of Immunology

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The majority of the human population becomes infected early in life by the gammaherpesvirus Epstein Barr Virus (EBV). Some findings suggest that there is an association between EBV infection and the appearance of pathogenic antibodies found in Lupus. Gammaherpesvirus 68 infection of adult mice (an EBV model) has been shown to induce polyclonal B cell activation and hypergammaglobulinemia, as well as increased production of autoantibodies. Here we explored the possibility that this breach of tolerance reflects loss of B cell anergy. Our findings show that although anergic B cells transiently acquire an activated phenotype early during infection, they do not become responsive to autoantigen as measured by the ability to mobilize Ca2+ following antigen receptor crosslinking or mount antibody responses following immunization. Indeed, naïve B cells also acquire an activated phenotype during acute infection, but are unable to mount antibody responses to either T-dependent or T-independent antigens. In acutely infected animals, antigen stimulation leads to upregulation of costimulatory molecules and relocalization of antigen-specific B cells to the B-T cell border, however, these cells do not proliferate or differentiate into antibody secreting cells. Adoptive transfer experiments show that the suppressed state is reversible and is dictated by the environment in the infected host. Finally, B cells in infected mice deficient of CD4+ T cells are not suppressed, suggesting a role for CD4+ T cells in enforcing unresponsiveness. Thus rather than promoting loss of tolerance, gammaherpesvirus 68 infection induces an immunosuppressed state, reminiscent of Compensatory Anti-inflammatory Response Syndrome (CARS).

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Section: Discussionmentioning

confidence: 99%

Retention of Anergy and Inhibition of Antibody Responses during Acute Gammaherpesvirus 68 Infection

Getahun

Smith

Kogut

et al. 2012

The Journal of Immunology

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“…The origin, maintenance, and handling of T. musculi in our laboratory have been thoroughly described (22,23 vestigation (12), from which it was learned that a parasite infection provides a powerful stimulus, at least as effective as injection of poly(IC) or, in comparison to other reports, as effective as bacterial endotoxin, Newcastle disease virus (24), or carrageenan (25) vis-a-vis NK stimulation.…”

Section: Methodsmentioning

confidence: 99%

“…The origin, maintenance, and handling of T. musculi in our laboratory have been thoroughly described (22,23). Mice received 5 x 105 viable trypanosomes at inoculation, and were sacrificed at appropriate times thereafter.…”

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confidence: 99%

Age-associated impairment of murine natural killer activity.

Albright¹,

Albright²

1983

Proc. Natl. Acad. Sci. U.S.A.

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Natural cell-mediated cytotoxicity may be critical in. the resistance displayed by animals.and humans to tumors and various pathogenic microorganisms. Because the frequency of tumors and infections increases markedly in aging populations, we have compared the natural killer (NK) competence of lymphid tissues (spleen, bone marrow) and of peritoneal cells of young adult and aged mice. Spontaneous NK activity was much lower, and the rate of. target cell lysis was much less, in aged mice. The level of NK activitywas only modestly increased in old, compared to young, mice when they were exposed to Trypanosoma. muscwli, an organism that provides strong stimulation of NK activity. Restricted NK activity of aged mice was not attributable to suppressor cells. The NK effector cells in old mice were characterized as being nonadherent to plastic, completely susceptible to lysis by complement plus an antiserum against specificity NK 1.2, and only slightly affected by treatment with antiserum against specificity Thy-1.2. Two indirect methods were employed to assess the-relative frequency of splenic NK cells at the time of-maximal stimulation by T. musculi: a cytotoxicity assay-with antiserum against NK 1.2 and a binding assay involving monolayers of YAC-1 tumor target cells. Similar results were obtained in both assays, indicating that at maximal stimulation about 10% of the total spleen cells of both young and old mice were NK cells. We conclude (cautiously) that the functional efficiency of aged NK cells is impaired and that this -defect may account, in part, for reduced ability of aged individuals to resist certain types of cancer and certain pathogenic microorganisms.Many biological and medical scientists believe that the declining competence of the immune system is responsible, in part, for the progressive rise in the frequency of. neoplastic and infectious. diseases associated with biological aging. The veracity of this postulate could be better judged if more were known about the immunological processes involved in responses to, and reactions with, tumor cells and pathogenic organisms. One feature of the immune system that has received considerable -attention in recent years is that of spontaneous, or natural, cellmediated cytotoxicity, associated especially with the subset of lymphocytes termed "natural killer" (NK) (1, 2). A variety of tumors (3, 4) and several pathogens (5-7) have been found to be susceptible to NK cells. The most clear-cut example of the susceptibility of a pathogen to NK cells is that of the human pathogen Trypanosoma cruzi (7). In addition, a number of other protozoan parasites have been found to alter markedly the NK activity of lymphoid tissues of their hosts (8-12).At present, information about the status of NK cells and their functional capabilities in aging animals and humans is meager. In most strains of mice,-NK activity in lymphoid tissues is high-.est in mice that are 1-3 months of age and declines considerably thereafter (13)(14)(15). Little is known about-NK cells and activity...

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“…Trypanosomes. The origin and maintenance of the line of T. musculi used in our laboratory have already been reported (1). The line of trypanosomes has been maintained by weekly passage in normal mice and replaced at irregular intervals from stock kept frozen in liquid nitrogen.…”

Section: Methodsmentioning

confidence: 99%

The liver as a major site of immunological elimination of murine trypanosome infection, demonstrated with the liver perfusion model

1990

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The isolated liver perfusion model has been used to investigate immunological elimination of bacteria and yeasts but not for analysis of mechanisms of immunological destruction of extracellular parasitic protozoa. Extracellular trypanosomes are eliminated primarily through antibody (and complement?)-promoted hepatic 1965 on July 31, 2020 by guest http://iai.asm.org/ Downloaded from cific determinants in fibronectin.

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Mechanisms of trypanosome-mediated suppression of humoral immunity in mice

Abstract: Spleen cells from Trypanosoma musculiinfected mice were unable to respond to sheep erythrocyte antigen in vitro; moreover, they suppressed the responses of normal spleen cell cultures in dose-dependent fashion.

Cited by 25 publications

References 24 publications

Retention of Anergy and Inhibition of Antibody Responses during Acute Gammaherpesvirus 68 Infection

Retention of Anergy and Inhibition of Antibody Responses during Acute Gammaherpesvirus 68 Infection

Age-associated impairment of murine natural killer activity.

The liver as a major site of immunological elimination of murine trypanosome infection, demonstrated with the liver perfusion model

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