You observe that your patients treated by a soluble form of the CD28 co-stimulat

Question

You observe that your patients treated by a soluble form of the CD28 co-stimulatory molecule (that is expressed on T cells) experience prolonged allogeneic kidney graft survival. The very likely mechanism(s) involved in this effect of soluble CD28 include [assess the described hypothetical mechanisms (32-35) as either factually correct (= true) or incorrect (= false)]:

32. Binding of soluble CD28 to B7 family members on dendritic cells (DCs) causes the DCs to migrate to lymph nodes where they meet up and interact with naïve T cells, which delays migration of host T cells to the graft.

33. Binding of soluble CD28 to B7 family members on DCs interferes with DC production of IL-12, resulting in the polarization of naive T cells towards a TH2 phenotype that is not associated with cytolytic responses.

34. Binding of soluble CD28 to B7 family members on DCs prevents naïve T cells from getting activated, and this inhibits them from becoming effector cells that attack the graft.

35. Soluble CD28 binds to co-stimulatory ligands present on cells in the transplanted tissue and thus prevents effector T cells that have invaded the graft from receiving the signals needed to attack the foreign tissue.

Explanation / Answer

32=false

33=true

34=true

35=false

CD28 costimulatory pathway is probably most important for naive T cell activation. Upon engaement with its ligands CD28 provides costimulatory signal triggering survival ,proliferation and cytokine production of T cells.

CD28/B7 ligation in presence ofTCR stimulation increases expression of IL2 receptor Alpha chain(CD25) and of CD40 ligand and induces cytokine production including IL2 and imterferon . IL2 /CD25 binding initiates T cell proliferation. TCR stimulation in absence of CD28 induces classical T cell anergy . Anergic T cells are functionally inactivated with reduced proliferation , differentiation and cytokine production thereby increasing short term survival rates for renal grafts

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