Suppression of Graft-Versus-Host Reaction in Severe Combined Immunodeficiency with Maternal-Fetal T Cell Engraftment

Vaidya, Smita; Mamlok, Robert J.; Daeschner, Charles W.; Williams, J.; Ruth, J.; Goldblum, Randall M.

doi:10.1097/00043426-199122000-00013

Cited by 7 publications

(8 citation statements)

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“…However, 2 recent studies have also found evidence of maternal cells in the fetal circulation in elective terminations in early and late gestation (19,20). Maternal cells are known to engraft and persist in the circulation of infants with severe combined immunodeficiency (4,(21)(22)(23)(24)(25)(26). However, to our knowledge, no previous study has specifically examined longterm persistence of maternal cells in immunologically competent offspring.…”

Section: Discussionmentioning

confidence: 99%

Microchimerism of maternal origin persists into adult life

Maloney¹,

Smith²,

Fürst³

et al. 1999

J. Clin. Invest.

413

302

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Section: Discussionmentioning

confidence: 99%

Microchimerism of maternal origin persists into adult life

Maloney¹,

Smith²,

Fürst³

et al. 1999

J. Clin. Invest.

413

302

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“…In SCID fetuses (Piotrowski and Croy, 1996) and RAG-2 null ␥ c null (deficient T, B, and natural killer cell development; our unpublished observations), ROSA26 maternal cells had widespread, multiorgan localization beginning in gd 12.5 fetal thymus. In both immune-deficient strains, maternal cells of lymphoid appearance were present, presumably including T cells, based on literature demonstrating human maternal T cells in SCID offspring (Conley et al, 1984;Flomenberg et al, 1983;Pollack et al, 1982;Suda et al, 1984;Vaidya et al, 1991). In CD1 fetuses, thymic chimerism might be impeded by immune-related mechanisms or by physical space restriction imposed by developing lymphocytes that are occupying the available niches.…”

Section: Discussionmentioning

confidence: 99%

“…These transplacentally acquired cells are functionally competent, as evidenced by their ability to induce graft-versus-host disease in some patients (Conley et al, 1984;Flomenberg et al, 1983;Le Deist et al, 1987;Suda et al, 1984;Vaidya et al, 1991). Maternal cell transfer to immune-deficient fetuses has also been reported in studies using xenogeneically engrafted scid/scid (SCID) mice.…”

mentioning

confidence: 99%

Chimerism of Murine Fetal Bone Marrow by Maternal Cells Occurs in Late Gestation and Persists into Adulthood

Marleau

Greenwood

Wei

et al. 2003

Laboratory Investigation

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SUMMARY:Studies of murine severe combined immune-deficient (scid/scid) fetuses gestating in transgene-tagged immune competent dams have established high frequencies of transplacental trafficking of nucleated maternal cells. Maternal cells first appeared in thymus at gestation day (gd) 12.5 and were present in more than 90% of late gestation fetuses. Morphologically heterogeneous maternal cells were located predominantly in bone marrow and thymus and also occasionally in liver, spleen, and nonlymphoid organs. We have now evaluated maternal cell chimerism in offspring with normal lymphoid development. Genetically normal blastocysts from random-bred CD1 mice were transferred to C57BL/6J-lacZ transgene-tagged ROSA26 females. Serial sectioning of fetuses followed by histochemistry for lacZ-expressing cells was used to comprehensively define organs containing maternal cells. Fetuses, sectioned in their entirety, had no detectable maternal cells before gd 16.5. Morphologically homogenous, nucleated maternal cells were first present in fetal bone marrow cavities at gd 16.5 and were evident in all offspring in later gestation. Postnatally, maternal cells were also present in bone marrow cavities into adulthood, as determined by lacZ histochemistry and PCR amplification of the maternal transgene. The frequency of maternally derived cells in postnatal bone marrow was increased compared with late gestation, and occasionally, maternal cells were detected in postnatal spleen. The normalcy of maternal cell transfer to genetically immune competent progeny and their long-term engraftment is suggestive of a functional role for maternal cells in offspring. (Lab Invest 2003, 83:673-681).

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“…The residual function and the diversified repertoire of the autologous cells contributed to the excellent clinical status of the reported patient who had no obvious signs suggestive of OS. Similarly, it was speculated by others that the immunosuppressive effect of the maternal cells could modify the clinical symptoms associated with GVHD and cause them to be less severe than the skin manifestations characteristically observed in OS (Vaidya et al 1991).…”

Section: Introductionmentioning

confidence: 94%

Self-reactive and transplacental-acquired maternal T cells in SCID patients—time to update

Somech

2015

LymphoSign Journal

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Patients with severe combined immunodeficiency (SCID) typically present with profoundly reduced T cells. In some cases, however, T cells may be affected by defects that allow some T-cell development but compromise T-cell function such as in Omenn syndrome (OS), which is characterized by impaired Tcell differentiation in the presence of abnormal self-reactive cells. One distinctive feature of SCID patients, which can sometimes resemble the clinical picture of OS, is the presence of alloreactive cells that originated from transplacentally acquired maternal T lymphocytes. The traditional view is that self-reactive cells and transplacentally acquired maternal T cells cannot occur concomitantly in the same OS patient. This review provides an updated functional characterization of transplacentally acquired maternal T cells and compares them with the T cells of an OS patient. An unusual case of an immunodeficient SCID patient with a mild OS phenotype is also presented. This patient had both self-reactive cells and transplacentally acquired maternal T cells, allowing us to simultaneously evaluate the function and tolerance capacities of both cell types. We propose that coexistence of autologous and maternal T cells in patients exhibiting mild OS symptoms was rejected because it had not been studied before and not because the cells are mutually exclusive. Moreover, taking into consideration the milder clinical phenotype associated with transplacentally acquired maternal T cells in SCID patients, we believe that these cells may provide some degree of immunity and prevent autoimmunity, even though they do not actually function to protect against infections. Statement of novelty:Autologous and transplacental-acquired maternal T cells can coexist in the same SCID patient. Although both cell types are nonfunctional for protecting against infections, maternal cells provide some degree of immunity and therefore are associated with only mild GVHD symptoms.

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Suppression of Graft-Versus-Host Reaction in Severe Combined Immunodeficiency with Maternal-Fetal T Cell Engraftment

Cited by 7 publications

References 0 publications

Microchimerism of maternal origin persists into adult life

Microchimerism of maternal origin persists into adult life

Chimerism of Murine Fetal Bone Marrow by Maternal Cells Occurs in Late Gestation and Persists into Adulthood

Self-reactive and transplacental-acquired maternal T cells in SCID patients—time to update

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