**7. Adaptive immunity abnormalities in GCA**

The differentiation and activation of DCs (following stimulation via their TLRs) induces the subsequent recruitment of T cells into the vessel wall. Indeed, several studies on activation patterns and inflammatory mediators in GCA, have confirmed that the progression of the immune response is totally dependent on CD4+ T cells. [33] These cells are able to orchestrate the stimulation of macrophages that lead to vessel response to injury, resulting in luminal stenosis or wall destruction and aneurysm formation.

Upon antigen recognition, CD4+ T cells are activated and differentiated into effector and memory T cells, while the antigen-specific subpopulation is 10 to 100-fold expanded. Under physiological conditions, only a few antigen-specific memory T cells are capable to persist indefinitely and provide life-long protection against pathogens. In parallel, these memory cells comprise the main barrier against the elimination of T-cell mediated autoimmune responses.

In GCA, several efforts to recognize a single antigen that may initiate the pathogenic specific immune response have not been fruitful. [20] In accordance, attempts to isolate the T cell clone, which is responsible for the vascular pathology in the disease, have suggested more hetero‐ geneity than expected. Studies focusing on T cell receptor V genes in the arterial wall and the peripheral blood of GCA patients have arrived at the conclusion that the T cell repertoire is significantly biased. [34, 35] Sequence analysis of the CD4+ T cells isolated from the inflamed temporal arteries has strongly supported local T cell activation and expansion of only a few selected T cell specificities. Notably, T cells isolated from the right and left temporal arteries of the same patient utilized identical T cell receptors. [36]

More recent studies confirmed that multiple T cell lineages contribute to the disease process. Histopathologic analyses from temporal arteries, both prior to therapy and on therapy, convincingly proved that two cell lineages, Th1 and Th17, infiltrate the vessel wall prior to therapy. [37] The concurrent presence of the two T cell lineages coincided closely with the stimulation of two distinct immune axes, an IL-12-IFN-γ axis and an IL-1-IL-23 axis. It seems that different APC signals are able to recruit either the IFN-γ-dependent or the IL-17-depend‐ ent arm of the adaptive immunity, thus raising the possibility that more than one instigator is involved in GCA. [21]
