Γδ T-cell Activation Research Articles

Effector functions and control of human γδ T-cell activation

Effector functions and control of human γδ T-cell activation

Differential activation requirements associated with stimulation of T cells via different epitopes of CD3.

A panel of monoclonal antibodies directed to different epitopes of porcine CD3 were employed to investigate stimulation requirements of porcine T lymphocytes. It was found that epitope specificity was an important property of the anti-CD3 antibodies that determined the requirements for T-cell proliferation. Thus, T-cell proliferation induced by triggering different CD3 epitopes showed three different requirements: (a) proliferation induced by the most insensitive epitope required both epitope ligation and some unknown additional signal(s); (b) proliferation induced by the most common epitopes only required epitope ligation, either by monocytes or by immobilization; (c) proliferation induced by the most sensitive epitope required neither epitope ligation nor participation of antigen-presenting cells (APC). These findings may help to explain the previous confusion over the requirements for T-cell activation through the CD3 pathway. Finally, the above conclusions apply only to alpha beta T cells, as porcine gamma delta T cells, either in bulk culture or isolated, did not proliferate in response to anti-CD3 stimulation. Therefore, the mechanism underlying gamma delta T-cell activation may be different from that of alpha beta T cells.

Activation of circulating γδ T-lymphocytes by autologous sperm from men sensitized to sperm

The in vitro proliferative responses to sperm of T-lymphocytes bearing the αβ or γδ form of the antigen receptor were investigated. Peripheral blood mononuclear cells from five men without antisperm antibodies and eight men with antisperm antibodies both on sperm and in serum were incubated for 72 h in the presence of an equal concentration of autologous live sperm, freeze-thawed sperm and heat-killed sperm. Prior to incubation and after 72 h, aliquots were applied to Teflon coated microscope slides, which were subsequently incubated with monoclonal antibodies to the β chain and δ chain of the human T-cell receptor. Urethral samples were cultured for bacteria and tested for Chlamydia trachomatis by direct staining and by ELISA. The four men with chlamydial infections had the highest concentrations of circulating γδ T-cells ( P = 0.0008). The concentration of γδ T-cells from men with antisperm antibodies increased 245% over the buffer control in response to live sperm ( P < 0.0001). Proliferation of γδ T-cells was also seen to a lesser extent in response to freeze-thawed ( P = 0.002) and heat killed ( P = 0.03) sperm. In contrast, γδ T-cells from men without antisperm antibodies proliferated only marginally (36%) in response to live sperm ( P = 0.05) and were unresponsive to non-viable sperm. Only from men sensitized to sperm were αβ T-cells responsive, to a small extent, to live sperm ( P = 0.04). Thus, in men with antisperm antibodies, peripheral γδ and αβ T-cells appeared to be sensitized to antigens on the surface of viable sperm. The immune response of γδ T-cells to sperm may be a useful in vitro system to examine the mechanism of γδ T-cell activation.