The paper reports a study of the morphofunctional activity of T-lymphocytes in response to the in vitro contact with calcium phosphate (CP) coating in the presence of the particles bearing antibodies against CD2, CD3, and CD28 antigens. VT1-0 titanium plates (10 × 10 × 1 mm3) with a double-sided microarc rough (Ra = 2–5 µm) CP coating were used as the model samples of the mineral matrix of the bone tissue. Magnetic particles (MACSiBeadTM T-cell Activation/Expansion Kit human) bearing antibodies to CD2, CD3, and CD28 antigens were used as a T-cell activator (TCA) simulating the signals produced by antigen-presenting cells (APCs). Mononuclear cells (MNCs) isolated from human blood (98.8% of CD45CD3+ cells) were cultured in the presence of samples with a CP coating and/or TCA (2 × 106 particles in 1.5 mL of nutritive medium in the proportion of 2 : 1 to cells) for 2 and 14 days. The CP coating and TCA triggered MNC culture adaptation in a synergic way via the mechanisms of hyperactivation and subsequent death of T-lymphocytes. Immune selection occurred through the accumulation of the naive CD45RA+/RO+ T-lymphocytes and memory T-cells with the simultaneous depletion of the CD4+ and CD8+ T-cell pool. The shift in the T-lymphocyte populations was observed together with the increase (after 48 h of culturing) in the cell secretion activity with its subsequent decrease by the 14th day of observation. CP coating sustained (compared with the cell culture grown on plastic) the secretion ability of Th1 (IL-12, TNFα, and IFNγ) and Th2 (IL-4, IL-6, IL-10, and IL-13) lymphocytes. At the same time, the prolonged TCA signal after the 48-h activation caused the depletion of T-cell secretion. The suggestion that the observed in vitro effects may play role in the switching of signaling between T-lymphocytes, APCs, and CP materials at the cell–foreign body interface, which may result in a change in the inflammation phase, development of immune tolerance, successful osseointegration of the implant, or bone tissue remodeling impairment, is discussed.