scholarly journals Adaptive differentiation of murine lymphocytes. I. Both T and B lymphocytes differentiating in F1 transplanted to parental chimeras manifest preferential cooperative activity for partner lymphocytes derived from the same parental type corresponding to the chimeric host.

1978 ◽  
Vol 148 (3) ◽  
pp. 727-745 ◽  
Author(s):  
D H Katz ◽  
B J Skidmore ◽  
L R Katz ◽  
C A Bogowitz
Keyword(s):  
Bone Marrow ◽  
T Lymphocytes ◽  
B Lymphocytes ◽  
F1 Hybrid ◽  
Histocompatibility Complex ◽  
Self Recognition ◽  
Cooperative Activity ◽  
Selective Differentiation ◽  
Bone Marrow Chimeras ◽  
Adaptive Differentiation

The concept of adaptive (selective) differentiation preducts that early differentiation of lymphocytes is conditioned by the environment in which such differentiation takes place. These processes appear to involve selection of lymphocytes according to their self-recognition between interacting lymphocytes is, at least in part, controlled by major histocompatibility complex-linked genes, then adaptive differentiation is also controlled by these genes. In these studies, we have tested the capacities of helper T lymphocytes and hapten-specific B lymphocytes primed in the environments of various combinations of bone marrow chimeras prepared between two parental strains (i.e. A/J and BALB/c) and their corresponding F1 hybrid (CAF1) to interact with primed B and T lymphocytes derived from conventional parent and F1 donors as well as all of the corresponding bone marrow chimera combinations. The results demonstrate clearly that (a) F1 transplanted to F1 chimeric lymphocytes display no restriction in terms of cooperative activity with all of the various partner cell combinations; (b) parent transplanted to F1 chimeric lymphocytes manifest effective cooperative activity only for partner cells from F) or parental donors corresponding to the haplotype of the original bone marrow donor, thereby behaving phenotypically just like conventional parental lymphocytes; and (c) F1 transplanted to parent chimeric lymphocytes display restricted haplotype preference in cooperating best with partner lymphocytes sharing the H-2 haplotype, either entirely or codomimantly, of the parental chimeric host. The implications of these findings for understanding certain controlling mechanisms for lymphocyte differentiation are discussed.

scholarly journals Restricted helper function of F1 leads to parent bone marrow chimeras controlled by K-end of H-2 complex.

1978 ◽  
Vol 147 (6) ◽  
pp. 1838-1842 ◽  
Author(s):  
J Sprent
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
Parental Strain ◽  
T Helper ◽  
F1 Hybrid ◽  
Active Suppression ◽  
Helper Function ◽  
Bone Marrow Chimeras

F1 leads to parent bone marrow chimeras were prepared by transferring F1 hybrid marrow cells into heavily irradiated parental strain mice. When unprimed, donor-derived F1 T cells from the chimeras were activated to sheep erythrocytes (SRC) for 5 days in irradiated normal F1 mice, high IgM and IgG anti-SRC responses were observed with F1 B cells, and with B cells H-2-compatible with the strain in which the T cells were raised from stem cells. Significantly, however, responses with B cells of the opposite parental strain were either absent or very low. The restriction in T-helper function mapped to the K-end of the H-2 complex and could not be attributed to active suppression.

scholarly journals On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition?

1978 ◽  
Vol 147 (3) ◽  
pp. 882-896 ◽  
Author(s):  
R M Zinkernagel ◽  
G N Callahan ◽  
A Althage ◽  
S Cooper ◽  
P A Klein ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Cytotoxic T Cells ◽  
Thymic Epithelial Cells ◽  
Self Recognition ◽  
Specific Cytotoxicity ◽  
Restricted Activity ◽  
Bone Marrow Chimeras ◽  
Killer T Cells

In the thymus, precursor T cells differentiate recognition structures for self that are specific for the H-2K, D, and I markers expressed by the thymic epithelium. Thus recognition of self-H-2 differentiates independently of the T cells H-2 type and independently of recognition of nonself antigen X. This is readily compatible with dual recognition by T cells but does not formally exclude a single recognition model. These conclusions derive from experiments with bone marrow and thymic chimeras. Irradiated mice reconstituted with bone marrow to form chimeras of (A X B)F1 leads to A type generate virus-specific cytotoxic T cells for infected targets A only. Therefore, the H-2 type of the host determines the H-2-restricted activity of killer T cells alone. In contrast, chimeras made by reconstituting irradiated A mice with adult spleen cells of (A X B)F1 origin generate virus-specific cytotoxic activity for infected A and B targets, suggesting that mature T cells do not change their self-specificity readily. (A X B)F1 leads to (A X C)F1 and (KAIA/DC) leads to (KAIA/DB) irradiation bone marrow chimeras responded against infected A but not B or C targets. This suggests that cytotoxicity is not generated against DC because it is abscent from the host's thymus epithelium and not against DB because it is not expressed by the reconstituting lymphoreticular system. (KBIB/DA) leads to (KCIC/DA) K, I incompatible, or completely H-2 incompatible A leads to B chimeras fail to generate any measurable virus specific cytotoxicity, indicating the necessity for I-specific helper T cells for the generation of killer T cells. Finally adult thymectomized, irradiated and bone marrow reconstituted (A X B)F1 mice, transplanted with an irradiated thymus of A origin, generate virus-specific cytotoxic T cells specific for infected A targets but not for B targets; this result formally demonstrates the crucial role of thymic epithelial cells in the differentiation of anti-self-H-2 specificities of T cells.

Allo-Major Histocompatibility Complex–Restricted Cytotoxic T Lymphocytes Engraft in Bone Marrow Transplant Recipients Without Causing Graft-Versus-Host Disease

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 2999-3006 ◽  
Author(s):  
Liquan Gao ◽  
Tian-Hui Yang ◽  
Sophie Tourdot ◽  
Elena Sadovnikova ◽  
Robert Hasserjian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Cytotoxic T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Major Histocompatibility ◽  
Host Disease ◽  
Graft Versus Host ◽  
Histocompatibility Complex

Previous experiments in humans and mice have shown that allogeneic donors can serve as a source of cytotoxic T lymphocytes (CTL) specific for proteins, such as cyclin-D1 and mdm-2, expressed at elevated levels in tumor cells. In vitro, allo-major histocompatibility complex (MHC)–restricted CTL against these proteins selectively killed allogeneic tumor cells, including lymphoma, but not normal control cells. This suggested that these CTL may be useful for adoptive tumor immunotherapy, provided that they (1) survive in MHC-disparate hosts, (2) maintain their killing specificity, and (3) do not attack normal host tissues. Here, we used cloned allo-restricted CTL isolated from BALB/c mice (H-2d) that killed H-2b–derived tumor cells expressing elevated levels of the mdm-2 target protein. When these CTL were injected into bone marrow transplanted (BMT) C57BL/6 (H-2b) recipients, they consistently engrafted and were detectable in lymphoid tissues and in the bone marrow (BM). Long-term survival was most efficient in spleen and lymph nodes, where CTL were found up to 14 weeks after injection. The administration of CTL did not cause graft-versus-host disease (GVHD) normally associated with injection of allogeneic T cells. These data show that allo-restricted CTL clones are promising reagents for antigen-specific immunotherapy in BMT hosts, because they engraft and retain their specific killing activity without causing GVHD.

scholarly journals Evidence for the clonal abortion theory of B-lymphocyte tolerance.

1975 ◽  
Vol 141 (4) ◽  
pp. 904-917 ◽  
Author(s):  
G J Nossal ◽  
B L Pike
Keyword(s):  
Bone Marrow ◽  
Tissue Culture ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Cultured Cells ◽  
Bone Marrow Cells ◽  
Mouse Bone Marrow ◽  
Immune Competence ◽  
Self Recognition ◽  
Marrow Cells

This paper deals with the behavior of adult mouse bone marrow cells placed in tissue culture with or without antigen, and subsequently assessed for immune competence after adoptive transfer into lethally X-irradiated, syngeneic hosts. Attention was focussed on B lymphocytes through using hapten human gamma globulin (HGG) preparations as putative tolerogens in tissue culture, the T-cell-independent antigens DNP-POL and NIP-POL as challenge injections in adoptive hosts, and numbers of hapten-specific PFC in host spleens for the quantitation of immune competence. It was found that the capacity of bone marrow cells to mount an adoptive immune response rose by a factor of about fivefold over 3 days in tissue culture. This rise was completely abolished by the presence in the culture of hapten-HGG conjugates with about one mole of hapten per carrier molecule. The prevention of the emergence of immune competence amongst maturing B cells was termed clonal abortion tolerogenesis. Dose-response studies showed the lowest effective antigen concentration to be between 2.5 times 10- minus 10 and 2.5 times 10- minus 9 M, and a standard concentration of 2.5 times 10- minus 8 M was chosen as producing near maximal effects. The tolerance was antigen-specific and time-dependent, being maximal only when antigen was present continuously as the cultured cells was maturing. It did not depend on the presence of T lymphocytes in marrow, and was not of an "infectious" type. In contrast to tolerogenesis of mature B lymphocytes by high antigen concentrations, it could not be abolished by lipopolysaccharide. We speculate that clonal abortion may be a tolerance mechanism of great physiological significance for self-recognition, and discuss the results in the framework of other recent tolerance models, including those involving receptor blockade and suppressor T cells.

scholarly journals Dichotomy in the tissue origin of schistosome acquired class I and class II major histocompatibility complex antigens.

1984 ◽  
Vol 159 (3) ◽  
pp. 952-957 ◽  
Author(s):  
A Sher ◽  
D L Sacks ◽  
A J Simpson ◽  
A Singer
Keyword(s):  
Bone Marrow ◽  
Major Histocompatibility Complex ◽  
Class Ii ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Donor Cells ◽  
Bone Marrow Chimeras ◽  
Class Ii Antigens ◽  
Tissue Origin

Schistosoma mansoni schistosomula recovered from the lungs of mice have previously been shown to express host-derived class I and class II major histocompatibility complex (MHC) antigens. To investigate the tissue origin of parasite-acquired MHC products, lung-stage schistosomula were obtained from a series of parent leads to F1 and F1 leads to parent bone marrow chimeras and the parasites typed by immunofluorescence for the presence of haplotype-specific K region and I region MHC determinants. The results of these experiments indicated that, despite their intravascular residence in the host, schistosomula derive all of their class I antigen from a nonhemapoietic tissue source. In contrast, the class II antigens expressed on the surface of schistosomula were found to originate from bone marrow-derived donor cells. These results support the hypothesis that MHC product acquisition by schistosomes involves selective and specific interactions with host tissue and, in the case of class I antigens, suggest that the endothelium may be a major site of host molecule uptake for the parasite.

scholarly journals Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras.

1975 ◽  
Vol 142 (4) ◽  
pp. 989-997 ◽  
Author(s):  
H von Boehmer ◽  
L Hudson ◽  
J Sprent
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Parental Strain ◽  
Secondary Response ◽  
Cell Populations ◽  
Sheep Erythrocytes ◽  
Bone Marrow Chimeras

T-B collaboration has been studied in a secondary response to sheep erythrocytes using either syngeneic or allogeneic T- and B-cell combinations. T cells prepared from tetraparental bone marrow chimeras (TBMC), carrying H-2 determinants of one parental strain only, cooperated with syngeneic, as well as with allogeneic B cells carrying the alloantigens to which the T cells had been tolerized in the chimeric environment. When TBMC-derived cells of a single H-2 specificity were transferred with a mixture of TBMC-derived B cells of both H-2 types of the parental strains, no preference for syngeneic cooperation was found. The data therefore suggest that the presence of differing H-2-complex determinants on the allogeneic T- and B-cell populations of the two different strain combinations tested do not interfere with T-B collaboration when the cell populations studied are mutually tolerant.

scholarly journals Cytotoxic T lymphocyte responses by chimeric thymocytes. Self-recognition is determined early in T cell development.

1981 ◽  
Vol 153 (1) ◽  
pp. 13-29 ◽  
Author(s):  
A M Kruisbeek ◽  
R J Hodes ◽  
A Singer
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Third Party ◽  
Receptor Repertoire ◽  
Histocompatibility Complex ◽  
Self Recognition ◽  
Lymphocyte Responses ◽  
Bone Marrow Chimeras

In this study the cytotoxic T lymphocyte (CTL) recognition pattern of thymocytes from recently reconstituted parent leads to F1 and F1 leads to parent radiation bone marrow chimeras was investigated. Chimeric thymocytes were entirely of donor origin approximately 4 wk after irradiation and reconstitution but were not capable of autonomously generating either alloreactive or trinitrophenyl (TNP)-modified-self-reactive CTL responses. However, in the presence of interleukin-2 (I1-2), the the putative T helper cell product, CTL could be generated in vitro by thymocytes from recently reconstituted chimeras. Experiments with thymocytes from A leads to A X B and A X B leads to A chimeras revealed the following: (a) thymocytes from both types of chimeras were nonreactive to either A or B parental major-histocompatibility complex (MHC) determinants even though they were alloreactive to third-party stimulator cells; and (b) thymocytes from these chimeras were restricted to the recognition of TNP in association with MHC determinants syngeneic to the chimeric host. Thus, these experiments demonstrate that even at the earliest time CTL effectors of donor origin from the thymuses of chimeras can be studied, their self-receptor repertoire has already been restricted to recognition of host MHC determinants. These results support the concept that the host environment influences the self-recognition capacity of T cells at the pre- or intrathymic stage of differentiation.

Hematopoietic Reconstitution of Mice Cord Blood Transplantation Combined with Bone Marrow Transient Hematopoietic Progenitor Cell

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4688-4688
Author(s):  
Jun Shi ◽  
Kazuma Ikeda ◽  
Maeda Yosinobu ◽  
Yinghua Yuan ◽  
Yehua Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Lymphocytes ◽  
Cord Blood ◽  
Progenitor Cells ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Immune Reconstitution ◽  
Hematopoietic Progenitor Cell ◽  
Fetal Blood

Abstract Abstract 4688 Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. However, fetal blood recipients had slower hematopoietic engraftment and impaired immune reconstitution. To accelerate myeloid and lymphoid recovery, we used an animal model of newborn blood modeled for cord blood (CB), along with transiently reconstituting progenitor cells from congenic bone marrow with recipients, as sources of stem cells. According to the previous reports that murine transiently reconstituting progenitor cells express the c-kit molecule, but not Sca-1 and lymphohematopoietic lineage markers, Lin-sca-1-c-kit+(c-kit+) were isolated by MACS method. c-kit+ cells population consisted of exclusively of medium- or large-sized blast-like cells, which displayed relatively low proliferative potential in vitro than Lin-sca-1+ (sca-1+) population. After transplantation of CB from DBA/2 mice (H-2d/d, CD45.2), with or without graded numbers of either c-kit+ or sca-1+ cells isolated from BDF1 mice (H-2d/b, CD45.1) bone marrow into lethally irradiated CD45.2 congenic BDF1 mice, hematopoietic engraftment were dynamic investigated. The intermingled transplantation of CB and c-kit+ cells or sca-1+ cells at the dosages of 1×104 or 2.5×104 or 5×104 to recipient mice leads to the quantity of white blood cells and platelets increased to 1×109/L and 1×1012/L at day12, whereas the injection of CB alone resulted in day17. By 2 weeks post-transplantation, congenic BM-derived cells were dominantly found in granulocytes and B lymphocytes, while host cells were dominantly found in T lymphocytes in CB transplantation combined either with c-kit+cells or sca-1+ cells. In cotransplantation with CB and c-kit+cells – engrafted surviving mice, the degree of donor CB cells in the peripheral blood increased progressively over time, while congenic donor BM-derived cells decreased gradually. After 60 weeks cotransplantation with CB and c-kit+ cells, a complete chimerism frequency of CB–derived cells continued to maintain in granulocytes and B lymphocytes, while T lymphocytes were dominantly derived from CB. On the other hand, congenic bone marrow or host-derived cells were the dominant population and CB-derived cells in the peripheral blood were less than 10% after 60 weeks cotransplantation with CB and sca-1+cells. In conclusion, the cotransplantation of CB and congenic c-kit+ cells was able to accelerate early hematopoietic recovery due to congenic marrow cells. But complete or main chimerism of cord blood was formed without or with fewer residual cells of host origin and congenic BM origin in long-term multilineage reconstitution. Thus, this cotransplant model in vivo may be to bring useful information for improving hematopoietic and immune reconstitution in fetal blood recipients. Disclosures: No relevant conflicts of interest to declare.

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