Correlation of Immunological Function With Splenic Histopathology During the Preclinical Stages of Host-Versus-Graft Syndrome in Par-Ent-F1 Mouse Chimeras

Hard, Richard C.

doi:10.1097/00007890-197406000-00011

Cited by 7 publications

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“…It is also possible that some B cells were activated by LPS, but could not proliferate because of decreased synthesis of B cell growth and maturation factors. Late in lethal HVG disease there are marked decreases in thymic-dependent antibody responses [8], and declines in serum IgGl levels [14] and in the percentages of mature F) donor antibody-forming cells [20] that may signal a waning of T cell help and decreased output of IL-6 [25]. In pilot studies, IL-4 was not detected in cultures of splenic or nodal cells from 21-day-old HVG mice.…”

Section: Discussionmentioning

confidence: 94%

“…Billingham & Brent [5] were probably the first to observe some features of lethal HVG disease when they noted 'gross splenomegaly' and 'conspicuously hypertrophied lymph nodes' in three of 15 A strain mice which died after neonatal inoculations of (C57xA)Fi spleen cells. In addition to lymphosplenomegaly [5][6][7], mice with the full blown, lethal syndrome have in vivo deficiencies in humoral [8] and cell-mediated [9] immunity, develop polyclonal hyperglobulinaemia with IgGl predominance [7,9] and rapidly form immune complexes which cause renal disease [7,10] and trigger disseminated intravascular coagulation [11]. Deaths occur in 30 days.…”

Section: Introductionmentioning

confidence: 99%

“…Deaths occur in 30 days. Immunopathologic studies indicate that donor T cells may be targets of the HVG reaction, and show that terminally ill mice have subnormal in vitro T-dependent immune responses [8,12]. The seeming paradox of how chimaeras with poor primary antibody responses can develop hyperglobulinaemia and immune complexes is explained by the demonstrations of a vigorous allogeneic effect on Fj donor B memory cells which engraft despite the HVG reaction, then proliferate and mature into antibody-forming plasmacytoid cells because of it [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Immunodeficiency in RFM/(T6xRFM)F1 mouse chimaeras with lethal host-versus-graft syndrome

Hard

Montour

Fuchs

1995

Clinical and Experimental Immunology

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SUMMARYRather than central tolerance, the perinatal inoculation of related F, hybrid spleen cells into inbred mice may result in host-ver.5M.y-graft (HVG) reactions manifested as transient autoimmunity, or as a lethal immunodeficiency syndrome. RFM/(T6xRFM)Fi chimaeras with lethal disease die in 30 days with lymphosplenomegaly, immune complexes and impaired immune responses. The present studies used in vitro proliferation assays to show that the HVG reaction caused hyperplasia sufficient to account for the lymphosplenomegaly, while also causing severe impairment of splenic and nodal cell responses to concanavalin A (Con A) and to bacterial lipopolysaccharide (LPS). By 25 days, HVG mice could not distinguish between self and non-self as judged by mixed lymphocyte reactions (MLR) to RFM, (T6xRFM)Fi and third party A/J cells. There were no indications that host cells reactive to Fi donor cells had undergone clonal deletion, anergy or expansion. Flow cytometry revealed that donor T lymphocytes achieved stable engraftment, mostly in the nodes, despite the HVG reaction. Taken together with previous observations, these studies showed that HVG reactions in young parent F|/chimaeras can result in an immunodeficiency state which is characterized by an early appearing, profound and persistent impairment of both host and donor T and B cell functions. The results suggest that HVG reactions can contribute directly to immune deficits seen after clinical allogeneic bone marrow transplantation.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunodeficiency in RFM/(T6xRFM)F1 mouse chimaeras with lethal host-versus-graft syndrome

Hard

Montour

Fuchs

1995

Clinical and Experimental Immunology

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“…Taken together, these two findings indicated that Fl donor Bcells presensitized to antigen had somehow escaped the fate of donor and host T-cells and gone on to contribute to the elevated levels of serum immunoglobulins. Before these observations, it had been difficult to understand how hyperglobulinemia could develop in mice with HVG syndrome, because early studies had shown that host B-cells, and any donor B-cells that might have survived the HVG reaction, responded very poorly to primary challenge with thymus-dependent antigens (7,8,16). Studies just completed (14) have strongly buttressed the thesis suggested by the antiviral antibody studies, that primed Fl donor B-cells survived the allogenic HVG reaction and flourished because of it.…”

Section: Discussionmentioning

confidence: 99%

Expression of murine leukemia viruses in RFM mice with host versus graft disease after perinatal inoculation of (T6 X RFM)F1 lymphohemopoietic cells

Cross¹,

Brede²,

rd³

et al. 1983

Infect Immun

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Host versus graft disease is the fatal syndrome of altered immunity that follows the perinatal inoculation of related F1 hybrid spleen cells to susceptible strains of inbred mice. The allogenic reaction results in severe depletion of T-lymphocytes, but causes hyperplasia and hypersecretion of B-cells. Among the long-term survivors of acute host versus graft reactions, there is a high incidence of nonthymic lymphomas associated with ecotropic murine leukemia virus that may be of donor F1 origin. The present studies were done to determine whether ecotropic murine leukemia virus played any role in the pathogenesis of acute host versus graft disease in RFM mice perinatally inoculated with (T6 X RFM)F1 spleen cells. In RFM/(T6 X RFM)F1 chimeras, N-tropic murine leukemia virus can be detected as early as 3 days. The progression of the disease was accompanied by increasing viral expression. The inoculation of N-tropic virus of F1 donor origin into RFM neonates failed to induce disease, although the virus proliferated. Detection of progressively rising titers of antibody to murine leukemia virus linked the virus to the development of hyperimmunoglobulinemia by virtue of its ability to serve as a replicating source of antigens. These and other studies provided evidence that the seemingly paradoxical appearance of hyperimmunoglobulinemia in T-cell-deficient mice with the host versus graft syndrome is due, at least in part, to the stimulation of presensitized F1 donor B-cells, which are not destroyed in the allogenic reaction, as are the T-cells. Another unusual finding was the detection of polytropic murine leukemia virus in 25-day-old RFM/(T6 X RFM)F1 chimeras. It is suggested that the allogenic host versus graft reaction favored the formation of recombinants.

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Pathology, immunology and virology of the host versus graft syndrome

Hard

Cross

1983

Surv. immunol. Res.

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Correlation of Immunological Function With Splenic Histopathology During the Preclinical Stages of Host-Versus-Graft Syndrome in Par-Ent-F1 Mouse Chimeras

Cited by 7 publications

References 0 publications

Immunodeficiency in RFM/(T6xRFM)F1 mouse chimaeras with lethal host-versus-graft syndrome

Immunodeficiency in RFM/(T6xRFM)F1 mouse chimaeras with lethal host-versus-graft syndrome

Expression of murine leukemia viruses in RFM mice with host versus graft disease after perinatal inoculation of (T6 X RFM)F1 lymphohemopoietic cells

Pathology, immunology and virology of the host versus graft syndrome

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