Age-related changes in cell surface antigens of preleukemic AKR thymocytes.

Kawashima, Kohei; Ikeda, Hisami; Stockert, Elisabeth; Takahashi, Toshitada; Old, Lloyd J.

doi:10.1084/jem.144.1.193

Cited by 76 publications

(38 citation statements)

References 26 publications

(13 reference statements)

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“…27,37,38 Here, we described the specific stages of thymic development at which leukemic thymocytes accumulate. These stages belong to an early T-cell compartment, revealed by the distribution of CD44 versus CD25 expression.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of IL-7Rα provides a competitive advantage during early T-cell development

Laouar

Flavell

2004

Blood

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Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell antigen receptor. Although ␣␤ T-cell development is observed in IL-7-and IL-7R␣-deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R␣ that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R␣ was revealed by surface staining, and increased IL-7R␣ mRNA was documented by using reverse transcriptase-polymerase chain reaction ( IntroductionCritical checkpoints controlling early T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre-T-cell receptor (pre-TCR). 1 The early T-cell compartment accounts for 2% to 5% of the adult thymus and is mainly represented by the CD4 Ϫ CD8 Ϫ double-negative (DN) thymocytes. 2 DN thymocytes are conventionally fractionated into distinct developmental stages according to the distribution of CD44 versus CD25 markers. 3 Four developmental stages have been described in which DN thymocytes progress from CD44 ϩ CD25 Ϫ (stage I) to CD44 ϩ CD25 ϩ (stage II) to CD44 Ϫ CD25 ϩ (stage III), and finally to CD44 Ϫ CD25 Ϫ (stage IV) before they progress to the CD4 ϩ CD8 ϩ double-positive (DP) stage. Pre-TCR-mediated selection among DN cells for productive TCR␤ V(D)J rearrangements, also termed ␤-selection, has been associated with stage III cells. 4,5 Among stage III cells, one cell subset is represented by small-sized cells that either have not completed ␤ gene rearrangement or have out-of-frame rearrangements ("E" cells). The other subset consists of large-sized cells that are often in S phase and show in-frame ␤ chain gene rearrangements ("L" cells). The L fraction represents, therefore, cells that have productively rearranged their ␤ chain gene and expressed the pre-TCR. 4 Subsequently, signal through the pre-TCR serves as a first checkpoint in early T-cell development and is critical for further progression and differentiation. [6][7][8] Such progression and differentiation is, however, severely compromised unless there is signaling through the IL-7R.The IL-7R comprises the IL-7R␣ chain (CD127) and the common cytokine receptor ␥ chain (␥c, CD132) that is also a constituent of the IL-2, IL-4, IL-9, IL-15, and IL-21 receptors. 9 Although ␣␤ T-cell development is observed in IL-7-, IL-7R␣-, and ␥c-deficient mice, the number of thymocytes is significantly reduced, 10-12 implying a role for the IL-7R in controlling the size of the thymus. Nevertheless, the relationship between checkpoints mediated by IL-7R signals and pre-TCR is still controversial. Three broad kinds of models are that (1) IL-7R signaling has no link to ␤-selection, but just permits cell survival; (2) ␤-selection causes IL-7R␣ expression, and thus...

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Section: Discussionmentioning

confidence: 99%

Overexpression of IL-7Rα provides a competitive advantage during early T-cell development

Laouar

Flavell

2004

Blood

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“…Several independent approaches also suggest that MuLV are inserted as multiple copies into cell genomes in AKR and other mouse strains and inherited in a Mendelian fashion (Aaronson et al, 1971 ;Berns and Jaenish, 1976;Chattopadhyay et al, 1975Chattopadhyay et al, , 1976Lilly and Pincus, 1973;Lowy et al, 1971 ;Rowe, 1972;. Some, but not necessarily all, of these endogenous MuLV may be leukemogenic (Greenberger et al, 1975;Heiniger et al, 1976;Lilly et al, 1975 From several studies, the' resence of the thymus appears to be critical for murine lymphoid leukemia development and most evidence indicates that T lymphocytes are directly transformed in the thymic microenvironment (Declkve et al, 19756;Gross, 1970;Kaplan, 1974;Kawashima et al, 1976;Metcalf, 1966). It is therefore of obvious interest to examine more closely the expression of endogenous MuLV in thymus cells and its consequences.…”

Section: Secondly An Indirect Imrnunofluorescence (If)mentioning

confidence: 94%

Spontaneous and induced appearance of murine leukemia virus antigen containing cells in organ cultures of embryonic mouse thymus

Riesenfeld

Alm

1977

Intl Journal of Cancer

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The potential of embryonic thymus organ cultures for studies on relations of endogenous MuLV, lymphoid cells and thymic microenvironment to lymphoma development were evaluated. Four main findings are reported. First, thymuses of 14-day-old CBA and AKR embryos could be maintained in organ cultures for at least 9 weeks with sustained production of lymphocytes. Lymphopoiesis in CBA and AKR thymuses were not grossly different. Secondly, an indirect immunofluorescence (IF) technique demonstrated spontaneous appearance of MuLV-antigen-containing cells in AKR, but not in CBA thymuses. Such spontaneous MuLV expression first occurred after 16 days of organ culture, thereafter infrequently and at random in individual thymus cultures. Thirdly, incubation of AKR and CBA thymuses in lymphoma extract containing AKR-type MuLV at initiation of organ cultures induced MuLV-antigen-containing cells. These were first detected after 7-14 days in culture, somewhat earlier and initially more frequently in AKR than in CBA thymuses. In the former, induction was accompanied by a clear reduction in the number of lymphocytes per thymus. Fourthly, iododeoxyuridine (IdUrd) treatment of AKR thymuses on cultute day 0, 3 or 7 decreased the number of lymphocytes per thymus and induced appearance of MuLV-antigen containing cells, assayed 8-20 days later. The IdUrd effect was most marked on day 0, and decreased sucessively on days 3 and 7. IdUrd had a much slighter effect on CBA thymuses, causing a lower reduction in cell numbers and inducing few MuLV-antigen cells. These main results clearly demonstrate the potential usefulness of the organ culture system for studied on leukemogenesis. It may be directly applied to answer several questions raised by detailed findings in our study.

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“…Also, the rapidity with which SFFV (as contained with LLV-F in the FV complex) is able to induce a fatal erythroleukemia in both newborn and adult mice has limited attempts to unravel those pathogenic events which precede the development of leukemia and which might be characterized as preleukemia changes. This is in contrast to the LLV-F (5) and other MuLV model systems in which preleukemic syndromes have been defined (6,7), and in which xenotropic MuLV expression has been correlated with the onset of leukemia (8).…”

mentioning

confidence: 95%

“…With the knowledge that preleukemia in other MuLV systems may be associated with changes in the expression of viral (e.g., xenotropic MuLV gp70) and host (e.g., H-2 and Thy 1.2) cell surface antigens (6,8,24) and with the knowledge that FV-infected mice (25) and in vitro bone marrow cell cultures (26) either contain increased numbers or sustained proliferation ofpluripotent hemopoietic stem cells (CFU-S), we were desirous to know if the spleen cells obtained from SFFV ÷ mice expressed any detectable alteration in membrane surface markers. We elected to conduct cell transplantation studies because this would allow us to enumerate the frequency of CFU-S per SFFV + spleen, the transplantability of such cells, and their ability to protect lethally irradiated mice from hemopoietic death.…”

Section: Rejection Of Sffi~ Preleukemic Spleen Cells By Nonimmunized mentioning

confidence: 99%

Persistence and pathogenicity of defective Friend spleen focus-forming virus. Decreased transplantability of hemopoietic cells as a marker for preleukemic change.

Eckner¹,

Hettrick²

1979

The Journal of Experimental Medicine

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A latent form of persistent infection can be established in susceptible adult mice inoculated with a preparation of defective Friend spleen focus-forming virus (SFFV) purified free from standard leukemia-inducing helper virus (LLV-F). SFFV persistence was initially observed using an in vivo rescue technique in which SFFV could be directly rescued to form splenic foci of malignant erythropoiesis in mice. At approximately 30 d after virus inoculation however, SFFV could not be rescued after inoculation of LLV-F indicating that persistently infected (i.e., SFFV+) mice were either immume to exogenous helper virus or able to express SFFV-associated defective-interfering (DI) function(s). Persistent infection by SFFV was further documented using an in vitro rescue technique and ultimately resulted in the induction by SFFV of erythroleukemia in the absence of polycythemia or overt virus production. However, SFFV rescued by LLV-F from persistently infected normal and transformed hemopoietic cells was able to induce polycythemia in adult mice suggesting that this is a helper controlled property of the Friend virus complex. Transplantable SFFV-induced erythroleukemic cells could be retrieved from persistently infected yet histologically normal mice. The duration of SFFV persistence in normal spleen tissue suggests that the SFFV provirus resides in either a long-lived or pluripotent hemopoietic cell. Further, certain changes occurred, presumably in the membranes of persistently infected cells, which preceded the overt development of Friend leukemia and facilitated the definition of an SFFV preleukemic phase. Cell surface alterations were revealed using cell transfer techniques. Hemopoietic cells harboring a rescuable SFFV failed to proliferate when inoculated into lethally irradiated, syngeneic adult mice. In contrast, the transformed progeny of preleukemic cell populations and spleen cells transformed by FV complex (i.e., cells replicating both SFFV and LLV-F) were not rejected. This result suggests that histologically normal SFFV+ preleukemic cells express an antigen recognition site which is not present on overtly transformed cells and which may be a pertinent surveillance target for host anti-leukemogenic reactions.

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Age-related changes in cell surface antigens of preleukemic AKR thymocytes.

Cited by 76 publications

References 26 publications

Overexpression of IL-7Rα provides a competitive advantage during early T-cell development

Overexpression of IL-7Rα provides a competitive advantage during early T-cell development

Spontaneous and induced appearance of murine leukemia virus antigen containing cells in organ cultures of embryonic mouse thymus

Persistence and pathogenicity of defective Friend spleen focus-forming virus. Decreased transplantability of hemopoietic cells as a marker for preleukemic change.

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