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Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) mice.

Stanford WL, Haque S, Alexander R, Liu X, Latour AM, Snodgrass HR, Koller BH, Flood PM - J. Exp. Med. (1997)

Bottom Line: To better understand the function of Ly-6A, we used gene targeting to produce Ly-6A mice which are healthy and have normal numbers and percentages of hematopoietic lineages.However, T lymphocytes from Ly-6A-deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates.This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7455, USA.

ABSTRACT
Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved in activation of hematopoietic stem cells. Antibody cross-linking studies and antisense experiments have suggested that Ly-6A is a lymphocyte coactivation molecule. To better understand the function of Ly-6A, we used gene targeting to produce Ly-6A mice which are healthy and have normal numbers and percentages of hematopoietic lineages. However, T lymphocytes from Ly-6A-deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates. In addition, Ly-6A mutant splenocytes generate more cytotoxic T lymphocytes compared to wild-type splenocytes when cocultured with alloantigen. This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses. Moreover, T cells from Ly-6A-deficient animals exhibit a prolonged proliferative response to antigen stimulation, thereby suggesting that Ly-6A acts to downmodulate lymphocyte responses.

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Ly-6A  T cells sustain their proliferative response longer  than the wild-type T cells. Splenic T cells from 4-, 6-, and 8-mo old Ly-6A mutant and wild-type littermates were activated by cross-linking cell  surface CD3 and their proliferation rates were measured at 48, 72, and 98 h  by adding [3H]TdR to the cells 3 h before measuring [3H]TdR incorporation. Ly-6A−/− T cells proliferate at higher rates than the age-matched  wild-type T cells at all time points. The percent increase in [3H]TdR incorporation by mutant T cells over wild-type T cells was 159% at 48 h (P  <0.01), 272% at 72 h (P <0.06), and 994% at 96h (P <0.01).
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Figure 5: Ly-6A T cells sustain their proliferative response longer than the wild-type T cells. Splenic T cells from 4-, 6-, and 8-mo old Ly-6A mutant and wild-type littermates were activated by cross-linking cell surface CD3 and their proliferation rates were measured at 48, 72, and 98 h by adding [3H]TdR to the cells 3 h before measuring [3H]TdR incorporation. Ly-6A−/− T cells proliferate at higher rates than the age-matched wild-type T cells at all time points. The percent increase in [3H]TdR incorporation by mutant T cells over wild-type T cells was 159% at 48 h (P <0.01), 272% at 72 h (P <0.06), and 994% at 96h (P <0.01).

Mentions: A kinetics experiment was performed to determine the rate of proliferation at three different time points by splenic T cells from 4-, 6-, and 8-mo-old Ly-6A mutant and wild-type littermates (three mice from each group). T cells were activated by cross-linking cell surface CD3 and their proliferation rates were measured at 48, 72, and 98 h by adding [3H]TdR to the cells 3 h before measuring [3H]TdR incorporation. Fig. 5 demonstrates that Ly-6A−/− T cells proliferate at higher rates than the age-matched wild-type T cells at all time points. In fact, the Ly-6A T cells appear to sustain the proliferative response longer than the wild-type T cells; in other words, the percent increase in [3H]TdR incorporation by mutant T cells over wild-type T cells was 159% at 48 h (P <0.01), 272% at 72 h (P <0.06), and 994% at 96 h (P <0.01).


Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) mice.

Stanford WL, Haque S, Alexander R, Liu X, Latour AM, Snodgrass HR, Koller BH, Flood PM - J. Exp. Med. (1997)

Ly-6A  T cells sustain their proliferative response longer  than the wild-type T cells. Splenic T cells from 4-, 6-, and 8-mo old Ly-6A mutant and wild-type littermates were activated by cross-linking cell  surface CD3 and their proliferation rates were measured at 48, 72, and 98 h  by adding [3H]TdR to the cells 3 h before measuring [3H]TdR incorporation. Ly-6A−/− T cells proliferate at higher rates than the age-matched  wild-type T cells at all time points. The percent increase in [3H]TdR incorporation by mutant T cells over wild-type T cells was 159% at 48 h (P  <0.01), 272% at 72 h (P <0.06), and 994% at 96h (P <0.01).
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Related In: Results  -  Collection

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Figure 5: Ly-6A T cells sustain their proliferative response longer than the wild-type T cells. Splenic T cells from 4-, 6-, and 8-mo old Ly-6A mutant and wild-type littermates were activated by cross-linking cell surface CD3 and their proliferation rates were measured at 48, 72, and 98 h by adding [3H]TdR to the cells 3 h before measuring [3H]TdR incorporation. Ly-6A−/− T cells proliferate at higher rates than the age-matched wild-type T cells at all time points. The percent increase in [3H]TdR incorporation by mutant T cells over wild-type T cells was 159% at 48 h (P <0.01), 272% at 72 h (P <0.06), and 994% at 96h (P <0.01).
Mentions: A kinetics experiment was performed to determine the rate of proliferation at three different time points by splenic T cells from 4-, 6-, and 8-mo-old Ly-6A mutant and wild-type littermates (three mice from each group). T cells were activated by cross-linking cell surface CD3 and their proliferation rates were measured at 48, 72, and 98 h by adding [3H]TdR to the cells 3 h before measuring [3H]TdR incorporation. Fig. 5 demonstrates that Ly-6A−/− T cells proliferate at higher rates than the age-matched wild-type T cells at all time points. In fact, the Ly-6A T cells appear to sustain the proliferative response longer than the wild-type T cells; in other words, the percent increase in [3H]TdR incorporation by mutant T cells over wild-type T cells was 159% at 48 h (P <0.01), 272% at 72 h (P <0.06), and 994% at 96 h (P <0.01).

Bottom Line: To better understand the function of Ly-6A, we used gene targeting to produce Ly-6A mice which are healthy and have normal numbers and percentages of hematopoietic lineages.However, T lymphocytes from Ly-6A-deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates.This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7455, USA.

ABSTRACT
Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved in activation of hematopoietic stem cells. Antibody cross-linking studies and antisense experiments have suggested that Ly-6A is a lymphocyte coactivation molecule. To better understand the function of Ly-6A, we used gene targeting to produce Ly-6A mice which are healthy and have normal numbers and percentages of hematopoietic lineages. However, T lymphocytes from Ly-6A-deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates. In addition, Ly-6A mutant splenocytes generate more cytotoxic T lymphocytes compared to wild-type splenocytes when cocultured with alloantigen. This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses. Moreover, T cells from Ly-6A-deficient animals exhibit a prolonged proliferative response to antigen stimulation, thereby suggesting that Ly-6A acts to downmodulate lymphocyte responses.

Show MeSH
Related in: MedlinePlus