Calcium homeostasis change in CD4+ T lymphocytes from human peripheral blood during differentiation in vivo.

Resting naïve CD4+(CD45R0-)CD45RA+ T cells are sensitive to ionomycin. In contrast, resting CD4+(CD45RA-)CD45R0+ memory T cells show resistance to this Ca2+ ionophore. In the present study, the ability of activated T lymphocytes to respond to ionomycin during the transition from naïve precursors into memory T cells has been analyzed. Activated CD4+(CD45RA+)CD45R0+ T cells are always present both in human peripheral blood (HPB) and in the ionomycin-resistant (IR) fraction. Therefore, some activated T cells are resistant toward the Ca2+ ionophore. CD69 molecules are markers of the very early stage of T cell activation. However, CD4+CD69+ T cells have never been found in the IR fraction. Thus, the majority of CD4+ T lymphocytes at the early stage of activation are ionomycin-sensitive cells. The proportion of CD4+CD25+ T cells did not differ significantly in HPB and in the IR fraction. The presence of CD4+CD25+ T lymphocytes in the IR fraction reflects changes in the Ca2+-signaling pathway at this differentiation step of activated cells. Depending on the expression level of CD25 molecules, the population of CD4+CD25+ cells is divided in T-regulatory (CD25high) and proliferating (CD25low) subpopulations. The action of ionomycin results in a decrease in the portion of the CD4+CD25low T-cells, but it leads to an increase in the proportion of the CD4+CD25high T lymphocytes. Consequently, greater portion of CD4+CD25high T lymphocytes and smaller portion of CD4+CD25low T cells are IR cells. Expression of HLA-DR molecules can be used as the marker for the late activation step. The IR fraction is significantly rich in CD4+HLA-DR+ T lymphocytes in comparison to the blood of the same donor. The link between different differentiation steps of CD4+ T-lymphocytes and alterations in calcium ion homeostasis is discussed.