TY - JOUR
T1 - Stepwise activation of T cells. Role of the calcium ionophore A23187
AU - Geller, R. L.
AU - Gromo, G.
AU - Inverardi, L.
AU - Ferrero, E.
AU - Bach, F. H.
PY - 1987
Y1 - 1987
N2 - The calcium ionophore A23187, at a concentration of 1 μg/ml, is able to stimulate proliferation of freshly isolated peripheral blood lymphocytes, CD4+-enriched cells, or CD8+-enriched cells as measured by [3H]thymidine incorporation. This proliferation is accompanied by an increase in interleukin 2 (IL-2) receptor expression but not by a detectable up-regulation in (IL-2) production or the development of cytotoxicity. Proliferation can be blocked by anti-CD3, CD4, or CD8 monoclonal antibodies, but not by anti-Tac. If CD8+-enriched cells are activated for 3 days with A23187 and the blasts present on day 3 are sorted and returned to culture, they rapidly develop cytolytic activity in the presence of recombinant IL-2 but not recombinant interferon-γ. CD4+ enriched cells, after activation with A23187, do not become cytotoxic in the presence of either recombinant IL-2 or recombinant interferon-γ. These findings permit study of the stepwise maturation of T cells in this alternative pathway by using 'minimal signals' that do not, by themselves and as used in these studies, stimulate precursor Tc to mature to full effector cytotoxic function. These findings are consistent with the model that A23187 drives T cells only part way along a pathway of maturation and that an additional second signal must be given to effect maturation to cytotoxic status.
AB - The calcium ionophore A23187, at a concentration of 1 μg/ml, is able to stimulate proliferation of freshly isolated peripheral blood lymphocytes, CD4+-enriched cells, or CD8+-enriched cells as measured by [3H]thymidine incorporation. This proliferation is accompanied by an increase in interleukin 2 (IL-2) receptor expression but not by a detectable up-regulation in (IL-2) production or the development of cytotoxicity. Proliferation can be blocked by anti-CD3, CD4, or CD8 monoclonal antibodies, but not by anti-Tac. If CD8+-enriched cells are activated for 3 days with A23187 and the blasts present on day 3 are sorted and returned to culture, they rapidly develop cytolytic activity in the presence of recombinant IL-2 but not recombinant interferon-γ. CD4+ enriched cells, after activation with A23187, do not become cytotoxic in the presence of either recombinant IL-2 or recombinant interferon-γ. These findings permit study of the stepwise maturation of T cells in this alternative pathway by using 'minimal signals' that do not, by themselves and as used in these studies, stimulate precursor Tc to mature to full effector cytotoxic function. These findings are consistent with the model that A23187 drives T cells only part way along a pathway of maturation and that an additional second signal must be given to effect maturation to cytotoxic status.
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M3 - Article
C2 - 2826575
AN - SCOPUS:0023587875
VL - 139
SP - 3930
EP - 3934
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -