NK Cell: An Unforgettable Lymphocyte (Comment on “Delayed Presentation of Severe Combined Immunodeficiency Due to Prolonged Maternal T Cell Engraftment”)

We report the outcome of allogeneic bone marrow transplantation (BMT) as treatment for severe combined immunodeficiency disease (SCID) in 31 patients grafted from 1968 until 1992. The patients received a graft from an HLA-identical related (n = 10), an HLA-haplo-identical related (n = 19), or a closely HLA-matched unrelated (n = 2) donor that resulted in the long-term survival of 6 of 10, 9 of 19, and 0 of 2 children, respectively. Major complications included failure of engraftment and early death caused by respiratory failure. The chimerism pattern and immunologic reconstitution were evaluated in 15 children who survived more than 1 year with sustained engraftment. The pattern of engraftment was investigated within flow-sorted peripheral blood (PB) T- and B-lymphoid, natural killer (NK), and myelomonocytic cell populations using the amplification of variable number of tandem repeats by the polymerase chain reaction. The immunologic reconstitution was assessed by various in vitro and in vivo parameters. Although the number of PB T cells and the in vitro T-cell proliferative response was in the lower region of normal in the majority of cases and even subnormal in some, in all cases donor T-cell engraftment and reconstitution of T-cell immunity was observed. Residual host-type T cells (1% to 5%) were detected in eight cases at multiple occasions. All children showed normal serum IgM and IgG subclass levels and produced specific IgG antibodies after vaccination, irrespective of donor B-cell engraftment. However, three HLA haplo-identical graft recipients with host-type B lymphoid and myeloid cells have a persistent selective IgA deficiency. NK cells were either of donor, host, or mixed origin. Donor NK cell engraftment restored defective in vitro NK cell function of the recipient. We conclude that determination of lineage-specific engraftment patterns provides valuable information for the understanding of the immunologic reconstitution after allogeneic BMT for SCID.

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Occult materno-foetal T-cell engraftment with a population of clonal TCRGD cells in an infant with T negative B positive severe combined immunodeficiency

Molecular Immunology ◽

10.1016/s0161-5890(98)90396-0 ◽

1998 ◽

Vol 35 (11-12) ◽

pp. 730

Author(s):

GENNERY

Keyword(s):

T Cell ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

Cell Engraftment

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Megadose CD34 + Cell Grafts Improve Recovery of T Cell Engraftment but not B Cell Immunity in Patients with Severe Combined Immunodeficiency Disease Undergoing Haplocompatible Nonmyeloablative Transplantation

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2008.07.008 ◽

2008 ◽

Vol 14 (10) ◽

pp. 1125-1133 ◽

Cited By ~ 40

Author(s):

Christopher C. Dvorak ◽

Giun-Yi Hung ◽

Biljana Horn ◽

Elizabeth Dunn ◽

Ching-Ying Oon ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

Cell Engraftment ◽

Cell Immunity ◽

Immunodeficiency Disease ◽

Severe Combined Immunodeficiency Disease ◽

B Cell Immunity

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Maternal T-Cell Engraftment Interferes With Human Leukocyte Antigen Typing in Severe Combined Immunodeficiency

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqv079 ◽

2016 ◽

Vol 145 (2) ◽

pp. 251-257 ◽

Cited By ~ 5

Author(s):

Chang Liu ◽

Brian Duffy ◽

Jeffrey J. Bednarski ◽

Cecelia Calhoun ◽

Lindsay Lay ◽

...

Keyword(s):

T Cell ◽

Human Leukocyte Antigen ◽

Severe Combined Immunodeficiency ◽

Human Leukocyte ◽

Combined Immunodeficiency ◽

Human Leukocyte Antigen Typing ◽

Leukocyte Antigen ◽

Cell Engraftment

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EBV-Negative, B-Cell Non-Hodgkin??s Lymphoma (B-NHL) in X-Linked Severe Combined Immunodeficiency (X-SCID): Remission With Engraftment of Donor T-Cell Engraftment

Journal of Pediatric Hematology/Oncology ◽

10.1097/01.mph.0000188519.25394.88 ◽

2005 ◽

Vol 27 (9) ◽

pp. 466 ◽

Cited By ~ 1

Author(s):

P Mustillo ◽

M Boyer ◽

A Termuhlen ◽

R Altura ◽

K Klopfenstein ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

Cell Engraftment

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In utero transfer of adult bone marrow cells into recipients with severe combined immunodeficiency disorder yields lymphoid progeny with T- and B-cell functional capabilities

Blood ◽

10.1182/blood.v86.11.4353.bloodjournal86114353 ◽

1995 ◽

Vol 86 (11) ◽

pp. 4353-4366 ◽

Cited By ~ 56

Author(s):

BR Blazar ◽

PA Taylor ◽

DA Vallera

Keyword(s):

T Cell ◽

B Cell ◽

Cell Function ◽

Severe Combined Immunodeficiency ◽

In Utero ◽

Combined Immunodeficiency ◽

Cell Engraftment ◽

Secondary Transfer

To determine if in utero transplantation could restore the immune system of mice with a severe combined immunodeficiency (SCID) disorder, C57BL/6Sz-scid/scid fetuses were injected on day 14/15 of gestation with adult congenic donor bone marrow (BM) cells. Congenic BM engrafted in one of eight (13%) recipients. Reconstitution of both lymphoid and nonlymphoid lineages was observed. In vitro and in vivo T-cell function was documented. Stem cells were shown to have engrafted by secondary transfer studies. When fully allogeneic C57BL/6 (H-2b) or B10.BR (H-2k) adult. BM cells were given to C.B-17-scid/scid (H-2d) fetal recipients, 15 of 54 (28%) recipients had evidence of engraftment, with up to 76% of peripheral blood (PB) being of in utero donor BM origin on day 131 postnatally. In all mice with persistent leukocyte engraftment, T- and B-lymphoid cells were entirely of donor origin. Donor T cells were tolerant to host but not third party alloantigens as measured in vitro. In vivo, T-cell function appeared intact. Although most mice had lower levels of B-cell engraftment than T-cell engraftment, mice with > or = 10% B cells were able to produce normal levels of IgM. Despite transplantation of fully allogeneic BM cells, stem cell engraftment could be demonstrated by secondary transfer of BM cells into lethally irradiated recipients that were congenic to the original in utero donor BM source. These data indicate that adult BM cells, even those fully allogeneic with the fetal recipient, can give rise to progeny with multilineage potential, which leads to restoration of T-cell and B-cell function.

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An expanded population of natural killer cells in mice with severe combined immunodeficiency (SCID) lack rearrangement and expression of T cell receptor genes.

Journal of Experimental Medicine ◽

10.1084/jem.164.5.1797 ◽

1986 ◽

Vol 164 (5) ◽

pp. 1797-1802 ◽

Cited By ~ 28

Author(s):

R J Lauzon ◽

K A Siminovitch ◽

G M Fulop ◽

R A Phillips ◽

J C Roder

Keyword(s):

T Cell ◽

Nk Cells ◽

T Cell Receptor ◽

Cell Function ◽

Nk Cell ◽

Severe Combined Immunodeficiency ◽

Cell Receptor ◽

Scid Mice ◽

Combined Immunodeficiency ◽

T Cell Receptor Genes

Mice with severe combined immunodeficiency syndrome (SCID) exhibit an impairment in both T and B cell maturation, whereas myelopoiesis remains unaffected. We report here that spleens from SCID mice have undergone phenotypic expansion of cells bearing the NK-2 and asialo GM1 markers (70-80%) characteristic of NK cells and this expansion is accompanied by a 3-4-fold enrichment in NK cytolytic activity over their normal C.B-17 littermates. Furthermore, the NK cells from SCID mice do not rearrange or express T cell receptor alpha or beta genes, or a third T cell rearranging gene, gamma. These findings suggest that (a) T cell receptors are not necessary for NK-mediated cytolysis, and (b) either NK cells constitute an entirely distinct lineage or NK cell function is acquired in pre-T cells prior to the expression of T cell receptor genes.

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