Naive T cells are positioned at the origin of adaptive immune responses. The activation of naive T cells is usually viewed from the perspective of IL-2 production and entry into the cell cycle. This activation is antigen specific and MHC restricted via TCR ligation/CD3 signaling but also demands the simultaneous ligation of and signaling via CD28. Naive T cell TCR ligation without appropriate co-stimulus produces an anergic state, in which the naive T cell fails to produce IL-2 or expand clonally. It is implied that cells that might present self-destructive antigens would be incapable of delivering required costimulus thus avoiding initiation of inappropriate immune responses. However, CD45RBhi expressing THP cells express high levels of CD40L that is sustained following extended periods of TCR/CD3 stimulation. CD40L is the major T cell molecule involved in contact-dependent signaling of both B-cell and macrophage effector functions. This suggests that naive CD4+ T cells are capable of participating in and contributing to on-going immune responses following signaling via TCR/CD3 alone. This dissertation represents efforts to analyze the contact signaling capability of naive CD4+ T cells and their ability to trigger macrophage cytocidal/tumoricidal functions.
The data generated by this research demonstrate that:
Naive T cells are positioned at the origin of adaptive immune responses. The activation of naive T cells is usually viewed from the perspective of IL-2 production and entry into the cell cycle. This activation is antigen specific and MHC restricted via TCR ligation/CD3 signaling but also demands the simultaneous ligation of and signaling via CD28. Naive T cell TCR ligation without appropriate co-stimulus produces an anergic state, in which the naive T cell fails to produce IL-2 or expand clonally. It is implied that cells that might present self-destructive antigens would be incapable of delivering required costimulus thus avoiding initiation of inappropriate immune responses. However, CD45RBhi expressing THP cells express high levels of CD40L that is sustained following extended periods of TCR/CD3 stimulation. CD40L is the major T cell molecule involved in contact-dependent signaling of both B-cell and macrophage effector functions. This suggests that naive CD4+ T cells are capable of participating in and contributing to on-going immune responses following signaling via TCR/CD3 alone. This dissertation represents efforts to analyze the contact signaling capability of naive CD4+ T cells and their ability to trigger macrophage cytocidal/tumoricidal functions.
The data generated by this research demonstrate that:
Naive T cells are positioned at the origin of adaptive immune responses. The activation of naive T cells is usually viewed from the perspective of IL-2 production and entry into the cell cycle. This activation is antigen specific and MHC restricted via TCR ligation/CD3 signaling but also demands the simultaneous ligation of and signaling via CD28. Naive T cell TCR ligation without appropriate co-stimulus produces an anergic state, in which the naive T cell fails to produce IL-2 or expand clonally. It is implied that cells that might present self-destructive antigens would be incapable of delivering required costimulus thus avoiding initiation of inappropriate immune responses. However, CD45RBhi expressing THP cells express high levels of CD40L that is sustained following extended periods of TCR/CD3 stimulation. CD40L is the major T cell molecule involved in contact-dependent signaling of both B-cell and macrophage effector functions. This suggests that naive CD4+ T cells are capable of participating in and contributing to on-going immune responses following signaling via TCR/CD3 alone. This dissertation represents efforts to analyze the contact signaling capability of naive CD4+ T cells and their ability to trigger macrophage cytocidal/tumoricidal functions.
The data generated by this research demonstrate that: