scholarly journals Graft-host tolerance in bone marrow transplant chimeras. Absence of graft-versus-host disease is associated with unresponsiveness to minor histocompatibility antigens expressed by all tissues

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3221-3228
Author(s):  
S Brochu ◽  
C Baron ◽  
R Belanger ◽  
C Perreault
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Marrow Transplant ◽  
Lymphoid Cells ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Cd8 Cells ◽  
B10 Cells

Because bone marrow (BM) transplantation is used with increasing frequency, it is important to elucidate the mechanisms involved in the establishment of tolerance to host minor histocompatibility antigens (MiHA) in recipients transplanted with T-cell-undepleted marrow grafts. We have previously shown that BM chimeras transplanted across MiHA barriers showed specific unresponsiveness to MiHA expressed on recipient-type concanavalin A blasts. Because expression of many MiHA is tissue-specific, we wanted to determine if chimera T lymphocytes would be tolerant to MiHA expressed by all host tissues and organs. To investigate this issue, we measured in vivo proliferation of lymphoid cells from normal C57BL/10 (B10) mice and (B10-->LP) chimeras in tissues and organs of lethally irradiated syngeneic and allogeneic recipients. Donor B10 cells were either untreated, or depleted with anti-Thy-1.2, anti-CD4, or anti-CD8 antibodies. Transplantation of B10 cells in LP recipients triggered an important T-cell-dependent 125I- dUrd uptake in several organs that involved both CD4+ and CD8+ cells. Using Thy-1-congeneic mice we showed that in long-term chimeras practically all CD4+ and CD8+ T lymphocytes were derived from hematopoietic progenitors and not from mature T cells present in the BM graft. When (B10-->LP) BM chimera cells were injected to secondary recipients, no proliferation was observed in any organ of LP hosts whereas normal proliferation was seen in H-2k allogeneic hosts. Thus, in these BM chimeras, tolerance encompasses MiHA expressed by all organs.

Graft-host tolerance in bone marrow transplant chimeras. Absence of graft-versus-host disease is associated with unresponsiveness to minor histocompatibility antigens expressed by all tissues

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3221-3228 ◽  
Author(s):  
S Brochu ◽  
C Baron ◽  
R Belanger ◽  
C Perreault
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Marrow Transplant ◽  
Lymphoid Cells ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Cd8 Cells ◽  
B10 Cells

Abstract Because bone marrow (BM) transplantation is used with increasing frequency, it is important to elucidate the mechanisms involved in the establishment of tolerance to host minor histocompatibility antigens (MiHA) in recipients transplanted with T-cell-undepleted marrow grafts. We have previously shown that BM chimeras transplanted across MiHA barriers showed specific unresponsiveness to MiHA expressed on recipient-type concanavalin A blasts. Because expression of many MiHA is tissue-specific, we wanted to determine if chimera T lymphocytes would be tolerant to MiHA expressed by all host tissues and organs. To investigate this issue, we measured in vivo proliferation of lymphoid cells from normal C57BL/10 (B10) mice and (B10-->LP) chimeras in tissues and organs of lethally irradiated syngeneic and allogeneic recipients. Donor B10 cells were either untreated, or depleted with anti-Thy-1.2, anti-CD4, or anti-CD8 antibodies. Transplantation of B10 cells in LP recipients triggered an important T-cell-dependent 125I- dUrd uptake in several organs that involved both CD4+ and CD8+ cells. Using Thy-1-congeneic mice we showed that in long-term chimeras practically all CD4+ and CD8+ T lymphocytes were derived from hematopoietic progenitors and not from mature T cells present in the BM graft. When (B10-->LP) BM chimera cells were injected to secondary recipients, no proliferation was observed in any organ of LP hosts whereas normal proliferation was seen in H-2k allogeneic hosts. Thus, in these BM chimeras, tolerance encompasses MiHA expressed by all organs.

Further evidence for H-2-unrestricted induction of minor histocompatibility antigens-specific T cell immunity in vivo

1988 ◽  
Vol 19 (1) ◽  
pp. 41-47
Author(s):  
K. Mizoguchi ◽  
K. Isobe ◽  
T. Yoshida ◽  
T. Iwamoto ◽  
T. Hasegawa ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Immunity ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Cell Immunity

scholarly journals Interleukin 2-activated killer cells in patients following transplants of soybean lectin-separated and E rosette-depleted bone marrow

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1893-1903 ◽  
Author(s):  
CA Keever ◽  
K Welte ◽  
T Small ◽  
J Levick ◽  
M Sullivan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells ◽  
Lak Activity

Abstract During the early period following bone marrow transplantation before the immune system has reached full functional maturity, unprimed, nonspecific lytic systems may play a critical role as antiviral or antitumor effectors. The reconstitution of cells with this potential is of particular importance in recipients of bone marrow that has been depleted of mature T lymphocytes to prevent graft v host disease (GVHD). We examined the recovery of natural killer (NK) cells and interleukin 2 (IL 2)-augmented lymphokine-activated killer cells (LAK) in 48 patients at various intervals following transplantation of bone marrow depleted of mature cellular elements by treatment with soybean agglutinin and sheep RBCs (SBA-E- BMT). We found normal levels of both NK and LAK activity as early as 3 weeks following SBA-E- BMT. When compared with cells from controls, NK and LAK precursors from transplant recipients appeared to be activated in vivo in that freshly isolated peripheral blood mononuclear cells (PBMCs) from patients had an elevated cytolytic activity toward NK-insensitive targets and a more rapid response to activation by IL 2. In patients as well as controls, both LAK precursors and LAK effectors lacked antigens present on mature T lymphocytes (CD3, CD4, or CD8) but expressed antigens present on NK cells (CD2, CD16, and NKH1A). The LAK cells did not lyse either donor or host peripheral blood T cell targets. The activity of NK effectors but not LAK precursors survived the in vivo total body irradiation used for pretransplant conditioning in three patients studied. LAK precursors could be demonstrated as early as 18 days following transplant at a time when the bone marrow contained primarily donor- derived cells. Little or no LAK activity could be generated from cells of the SBA-E- BM graft itself, suggesting that LAK precursors differentiate rapidly from more primitive progenitors in the marrow graft. Thus, our data indicate that the NK and LAK lytic systems are among the earliest activities to recover during immune reconstitution following T cell-depleted BMTs.

In Vivo Requirements for the Immune Recognition of L1210 Leukemia Cells by Allogeneic T-Lymphocytes

1983 ◽  
Vol 69 (5) ◽  
pp. 403-408
Author(s):  
Guido Forni ◽  
Luisa Lanfrancone ◽  
Mirella Giovarelli
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Immune Recognition ◽  
L1210 Leukemia ◽  
Simultaneous Presence ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens

The resistance of normal BALB/c mice (H-2d) against the L1210 Ha leukemia of DBA/2 mouse (H-2d) origin is due to the T-lymphocyte-dependent reaction towards DBA/2 multiple minor histocompatibility antigens (Mhas). These Mhas are displayed by the leukemic cells, though in a poorly immunogenic manner. The simultaneous presence of mitomycin C-inactivated DBA/2 leukocytes induces a significantly stronger T-lymphocyte-dependent reaction. This efficient presentation of target Mhas is restricted to Ia+ leukocytes. Their presence significantly increases BALB/c resistance, even when they are injected 3 days after the L1210 Ha challenge.

The Rapid Ex Vivo Generation of an Immunodominant Antigen-Specific Memory CD8 Population and Its Subsequent Homeostatic Expansion in Ablatively-Conditioned HCT Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3172-3172
Author(s):  
Melinda Roskos ◽  
Robert B. Levy
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Cell Populations ◽  
Cd8 Cells ◽  
Immunodominant Antigen ◽  
Transfer Strategies

Abstract There is currently significant interest in the transplant field to develop adoptive-transfer strategies utilizing T cell populations to provide immediate immune function as well as long-term immune reconstitution following hematopoietic cell transplantation (HCT). Presumably, these pre-selected T cell populations could then be further expanded in the transplant recipient as a consequence of lymphopenia-induced proliferation. However, clinical application of adoptive transfer strategies has been limited by practical (time, expense) and technical (isolation and expansion of antigen-specific T cell populations) difficulties, hence more efficient approaches need to be identified. Recent reports have demonstrated the feasibility for the rapid ex vivo generation of transgenic memory CD8 populations. We investigated the potential of applying this ex vivo approach to generate and expand an immunodominant antigen-specific memory population from primary CD8 T cells. CD8 cells recognizing the mouse H60 epitope were selected as the antigen-specific CD8 population. The H60 glycoprotein is the ligand for NKG2D and the LTFNYRNL peptide is an immunodominant minor transplantation antigen. H60 is expressed by BALB.B (H2b) hematopoietic cells and recognized by C57BL/6 (B6) CD8 cells within the context of the H2Kb molecule. CD8 T cells from normal B6 spleens were positively selected using Miltenyi beads. The purified CD8 cells (97%) were then cultured with bone marrow-derived B6 DC, rmIL-2, and H60 peptide (1μM) for 3 days. Cells were harvested and re-cultured with rmIL-15 for 2–4 days. The resultant CD8 population was enriched 10 fold for tetramer-stained H60+ CD8 T cells (average: 3.0% of CD8 T cells). The H60+ CD8 cells displayed a memory phenotype as characterized by CD44+, Ly6C+, CD62Lintermed, and CD25lo expression. We hypothesized these H60+ CD8 T cells could be further expanded in transplant recipients by lymphopenia-induced proliferation. To determine the expansion and persistence of H60+ TM post-HCT, H60+-enriched CD8 cells were co-transplanted with T cell-depleted B6 bone marrow into 9.0Gy-conditioned syngeneic recipients. The phenotype and number of H60+ cells in recipient spleens and bone marrow were assessed beginning 3 days post-HCT. Notably, the H60+ CD8 cells maintained their memory phenotype and persisted at least 2 months post-transplant. The ex vivo-generated H60+ TM underwent a relative expansion of 1.5–2 fold as assessed in recipient spleens, similar to the post-transplant expansion of H60+ CD8 TM derived in vivo from B6 mice primed to BALB.B cells. Moreover, this post-HCT expansion was also similar to that by an ex vivo-generated, transgenic CD8 TM population. Both (ex vivo and in vivo generated) H60+ TM populations also exhibited expansion (1.5–2 fold) in the bone marrow. In total, an immunodominant antigen-specific CD8 TM population was selectively generated and enriched ex vivo and found to undergo expansion following transplant into ablatively conditioned HCT recipients. The similarities in expansion and persistence between ex vivo generated H60 and in vivo primed H60 populations suggest this approach may have useful applications towards the development of successful adoptive transfer strategies.

Sign in / Sign up

Export Citation Format

Share Document