Contact-Dependent Activation of Macrophages by Naive CD4⁺ T cells.

<p>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, CD45RB^hi expressing T_HP 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.</p> <p>The data generated by this research demonstrate that:</p> <ol> <li>Naive T cell purification by endothelial panning was superior to the standard method of CD44 panning for studies on T cell mediated macrophage activation.</li> <li>The activation requirements for contact signaling of macrophages by naive T cells are less stringent than the requirements for activation of naive T cell proliferation.</li> <li>Viable naive T_HP and antigen presenting splenic macrophages are capable of delivering reciprocal activating signals.</li> <li>Viable naive T_HP responding to presented antigen were able to trigger IFNg-primed macrophages to produce nitric oxide by both CD40L-dependent and CD40L-independent signaling pathways.</li> </ol>

Name thesis:degree_name

PhD (Doctor of Philosophy)

Level thesis:degree_level

Dissertation - restricted

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.issued

2000

Author dc:creator

• Hoellman, John Richard

• macrophage activation
• cell contact-signaling
• naive CD4 T cells
• Biochemistry, Biophysics, and Structural Biology
• Life Sciences
• Medical Sciences
• Medicine and Health Sciences
• Microbiology

Statement dc:rights

• Copyright by the authors.

Repository record dc:identifier

https://dc.etsu.edu/etd/18

OAI identifier oai:identifier

oai:dc.etsu.edu:etd-1054