Calcium Homeostasis Change in CD4 super(+) T Lymphocytes from Human Peripheral Blood during Differentiation in vivo

• Published in: Biochemistry (Moscow) 2005-06, Vol.70 (6), p.692-702
• Main Authors: Khaidukov, S V, Litvinov, I S
• Format: Article
• Language: English
• ISSN: 0006-2979; 0320-9725
• DOI: 10.1007/s10541-005-0170-8

Resting naive CD4 super(+)CD45R0 super(-)CD45RA super(+) T cells are sensitive to ionomycin. In contrast, resting CD4 super(+)CD45RA super(-)CD45R0 super(+) memory T cells show resistance to this Ca super(2+) ionophore. In the present study, the ability of activated T lymphocytes to respond to ionomycin during the transition from naive precursors into memory T cells has been analyzed. Activated CD4 super(+)CD45RA super(+)CD45R0 super(+) 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 Ca super(2+) ionophore. CD69 molecules are markers of the very early stage of T cell activation. However, CD4 super(+)CD69 super(+) T cells have never been found in the IR fraction. Thus, the majority of CD4 super(+) T lymphocytes at the early stage of activation are ionomycin-sensitive cells. The proportion of CD4 super(+)CD25 super(+) T cells did not differ significantly in HPB and in the IR fraction. The presence of CD4 super(+)CD25 super(+) T lymphocytes in the IR fraction reflects changes in the Ca super(2+)-signaling pathway at this differentiation step of activated cells. Depending on the expression level of CD25 molecules, the population of CD4 super(+)CD25 super(+) cells is divided in T-regulatory (CD25 super(high)) and proliferating (CD25 super(low)) subpopulations. The action of ionomycin results in a decrease in the portion of the CD4 super(+)CD25 super(low) T-cells, but it leads to an increase in the proportion of the CD4 super(+)CD25 super(high) T lymphocytes. Consequently, greater portion of CD4 super(+)CD25 super(high) T lymphocytes and smaller portion of CD4 super(+)CD25 super(low) 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 super(+)HLA-DR super(+) T lymphocytes in comparison to the blood of the same donor. The link between different differentiation steps of CD4 super(+) T-lymphocytes and alterations in calcium ion homeostasis is discussed.