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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.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.

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.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.

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