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Superantigens increase the survival of mice bearing T cell lymphomas by inducing apoptosis of neoplastic cells.

Mundiñano J, Berguer PM, Cabrera G, Lorenzo D, Nepomnaschy I, Piazzon I - PLoS ONE (2010)

Bottom Line: Superantigens bind to major histocompatibility complex class II molecules and interact with T cells expressing a particular T cell receptor Vβ inducing a strong proliferation/deletion response of the superantigen-reactive T cells.However, there have been no attempts to investigate the ability of Sags to induce apoptosis in neoplastic T cells by signaling through the Vβ region of their TCR.The possibility of a therapeutic use of superantigens in lymphoma/leukemia T cell malignancies is discussed.

View Article: PubMed Central - PubMed

Affiliation: ILEX-CONICET, División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.

ABSTRACT
Superantigens bind to major histocompatibility complex class II molecules and interact with T cells expressing a particular T cell receptor Vβ inducing a strong proliferation/deletion response of the superantigen-reactive T cells. However, there have been no attempts to investigate the ability of Sags to induce apoptosis in neoplastic T cells by signaling through the Vβ region of their TCR. In the present study we show that bacterial and MMTV-encoded superantigens induce the apoptosis of AKR/J cognate lymphoma T cells both in vitro and in vivo. The Fas-Fas-L pathway was shown to be involved in the apoptosis of lymphoma T cells induced by bacterial superantigens. In vivo exposure to bacterial superantigens was able to improve the survival of lymphoma bearing mice. Moreover, the permanent expression of a retroviral encoded superantigen induced the complete remission of an aggressive lymphoma in a high percentage of mice. The possibility of a therapeutic use of superantigens in lymphoma/leukemia T cell malignancies is discussed.

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Sags increase the survival of cognate lymphoma-bearing mice.(A)T5 cells (5×103) or (B) T8 cells (5×103) were injected into the tail vein of AKR/J mice (n = 19 per group). At days 2 and 3, mice received an intraperitoneal injection of 50 µg of SEI or PBS. p = 0.0005, log-rank test. (C) T8.2 cells (1×103) or (D) T14 cells (1×103) were intravenously inoculated in AKR/J mice (n = 22 per group). At days 2 and 3 mice were intraperitoneally inoculated with 50 µg of SEB or PBS. Control mice were treated with PBS. p<0.0001, log-rank test. (E) T14 cells (1×103) were injected into the tail vein of MMTV BALB14-infected (n = 22) and MMTV BALB2-infected (n = 20) and non-infected (n = 20) AKR/J mice. p<0.0001, log-rank test. (F) T14 cells (1×103) were intravenously injected in AKR/J mice. Two days later, mice were infected as described in Materials and Methods with MMTV BALB14 (n = 22) or MMTV BALB2 (n = 22). Control mice received PBS (n = 22). p = 0.0123, MMTV- vs MMTV BALB14; p = 0.0075, MMTV BALB2 vs MMTV BALB14, log-rank test.
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pone-0015694-g007: Sags increase the survival of cognate lymphoma-bearing mice.(A)T5 cells (5×103) or (B) T8 cells (5×103) were injected into the tail vein of AKR/J mice (n = 19 per group). At days 2 and 3, mice received an intraperitoneal injection of 50 µg of SEI or PBS. p = 0.0005, log-rank test. (C) T8.2 cells (1×103) or (D) T14 cells (1×103) were intravenously inoculated in AKR/J mice (n = 22 per group). At days 2 and 3 mice were intraperitoneally inoculated with 50 µg of SEB or PBS. Control mice were treated with PBS. p<0.0001, log-rank test. (E) T14 cells (1×103) were injected into the tail vein of MMTV BALB14-infected (n = 22) and MMTV BALB2-infected (n = 20) and non-infected (n = 20) AKR/J mice. p<0.0001, log-rank test. (F) T14 cells (1×103) were intravenously injected in AKR/J mice. Two days later, mice were infected as described in Materials and Methods with MMTV BALB14 (n = 22) or MMTV BALB2 (n = 22). Control mice received PBS (n = 22). p = 0.0123, MMTV- vs MMTV BALB14; p = 0.0075, MMTV BALB2 vs MMTV BALB14, log-rank test.

Mentions: Intravenous injection of AKR/J lymphoma cells in 2 mo-old syngeneic mice caused disseminated and fatal lymphoma/leukemia. In order to evaluate whether Sags were able to increase the survival of lymphoma carrying mice T8.2, T8, T5 and T14 lymphomas were used. In a first set of experiments, AKR/J mice were intravenously inoculated with T5 or T8 cells and treated with SEI or PBS at days 2 and 3 after tumor inoculation. Figure 7A-B shows that SEI treatment was able to significantly increase the survival time of T5 lymphoma bearing mice (log-rank test, p = 0.0005). SEI did not affect the survival of mice bearing T8 cells.


Superantigens increase the survival of mice bearing T cell lymphomas by inducing apoptosis of neoplastic cells.

Mundiñano J, Berguer PM, Cabrera G, Lorenzo D, Nepomnaschy I, Piazzon I - PLoS ONE (2010)

Sags increase the survival of cognate lymphoma-bearing mice.(A)T5 cells (5×103) or (B) T8 cells (5×103) were injected into the tail vein of AKR/J mice (n = 19 per group). At days 2 and 3, mice received an intraperitoneal injection of 50 µg of SEI or PBS. p = 0.0005, log-rank test. (C) T8.2 cells (1×103) or (D) T14 cells (1×103) were intravenously inoculated in AKR/J mice (n = 22 per group). At days 2 and 3 mice were intraperitoneally inoculated with 50 µg of SEB or PBS. Control mice were treated with PBS. p<0.0001, log-rank test. (E) T14 cells (1×103) were injected into the tail vein of MMTV BALB14-infected (n = 22) and MMTV BALB2-infected (n = 20) and non-infected (n = 20) AKR/J mice. p<0.0001, log-rank test. (F) T14 cells (1×103) were intravenously injected in AKR/J mice. Two days later, mice were infected as described in Materials and Methods with MMTV BALB14 (n = 22) or MMTV BALB2 (n = 22). Control mice received PBS (n = 22). p = 0.0123, MMTV- vs MMTV BALB14; p = 0.0075, MMTV BALB2 vs MMTV BALB14, log-rank test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3008744&req=5

pone-0015694-g007: Sags increase the survival of cognate lymphoma-bearing mice.(A)T5 cells (5×103) or (B) T8 cells (5×103) were injected into the tail vein of AKR/J mice (n = 19 per group). At days 2 and 3, mice received an intraperitoneal injection of 50 µg of SEI or PBS. p = 0.0005, log-rank test. (C) T8.2 cells (1×103) or (D) T14 cells (1×103) were intravenously inoculated in AKR/J mice (n = 22 per group). At days 2 and 3 mice were intraperitoneally inoculated with 50 µg of SEB or PBS. Control mice were treated with PBS. p<0.0001, log-rank test. (E) T14 cells (1×103) were injected into the tail vein of MMTV BALB14-infected (n = 22) and MMTV BALB2-infected (n = 20) and non-infected (n = 20) AKR/J mice. p<0.0001, log-rank test. (F) T14 cells (1×103) were intravenously injected in AKR/J mice. Two days later, mice were infected as described in Materials and Methods with MMTV BALB14 (n = 22) or MMTV BALB2 (n = 22). Control mice received PBS (n = 22). p = 0.0123, MMTV- vs MMTV BALB14; p = 0.0075, MMTV BALB2 vs MMTV BALB14, log-rank test.
Mentions: Intravenous injection of AKR/J lymphoma cells in 2 mo-old syngeneic mice caused disseminated and fatal lymphoma/leukemia. In order to evaluate whether Sags were able to increase the survival of lymphoma carrying mice T8.2, T8, T5 and T14 lymphomas were used. In a first set of experiments, AKR/J mice were intravenously inoculated with T5 or T8 cells and treated with SEI or PBS at days 2 and 3 after tumor inoculation. Figure 7A-B shows that SEI treatment was able to significantly increase the survival time of T5 lymphoma bearing mice (log-rank test, p = 0.0005). SEI did not affect the survival of mice bearing T8 cells.

Bottom Line: Superantigens bind to major histocompatibility complex class II molecules and interact with T cells expressing a particular T cell receptor Vβ inducing a strong proliferation/deletion response of the superantigen-reactive T cells.However, there have been no attempts to investigate the ability of Sags to induce apoptosis in neoplastic T cells by signaling through the Vβ region of their TCR.The possibility of a therapeutic use of superantigens in lymphoma/leukemia T cell malignancies is discussed.

View Article: PubMed Central - PubMed

Affiliation: ILEX-CONICET, División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.

ABSTRACT
Superantigens bind to major histocompatibility complex class II molecules and interact with T cells expressing a particular T cell receptor Vβ inducing a strong proliferation/deletion response of the superantigen-reactive T cells. However, there have been no attempts to investigate the ability of Sags to induce apoptosis in neoplastic T cells by signaling through the Vβ region of their TCR. In the present study we show that bacterial and MMTV-encoded superantigens induce the apoptosis of AKR/J cognate lymphoma T cells both in vitro and in vivo. The Fas-Fas-L pathway was shown to be involved in the apoptosis of lymphoma T cells induced by bacterial superantigens. In vivo exposure to bacterial superantigens was able to improve the survival of lymphoma bearing mice. Moreover, the permanent expression of a retroviral encoded superantigen induced the complete remission of an aggressive lymphoma in a high percentage of mice. The possibility of a therapeutic use of superantigens in lymphoma/leukemia T cell malignancies is discussed.

Show MeSH
Related in: MedlinePlus