Tatiana and Alexander had normal levels of CD4 T cells but decreased levels of CD8 T cells. Their CD8 T cells were all γ:δ receptors rather than the normal α:β receptors, because α:β CD8 T cell maturation depends on MHC class I expression, which was deficient in Tatiana and Alexander. They had normal delayed-type hypersensitivity responses because these are mediated by CD4 T cells. They had high IgG levels because CD4 T cells help B cell maturation and antibody production, while CD8 T cells suppress these responses, and Tatiana and Alexander were deficient in CD8 T cells. Patients with TAP1/TAP2 deficiencies would have a similar clinical course as Tatiana
Tatiana and Alexander had normal levels of CD4 T cells but decreased levels of CD8 T cells. Their CD8 T cells were all γ:δ receptors rather than the normal α:β receptors, because α:β CD8 T cell maturation depends on MHC class I expression, which was deficient in Tatiana and Alexander. They had normal delayed-type hypersensitivity responses because these are mediated by CD4 T cells. They had high IgG levels because CD4 T cells help B cell maturation and antibody production, while CD8 T cells suppress these responses, and Tatiana and Alexander were deficient in CD8 T cells. Patients with TAP1/TAP2 deficiencies would have a similar clinical course as Tatiana
Tatiana and Alexander had normal levels of CD4 T cells but decreased levels of CD8 T cells. Their CD8 T cells were all γ:δ receptors rather than the normal α:β receptors, because α:β CD8 T cell maturation depends on MHC class I expression, which was deficient in Tatiana and Alexander. They had normal delayed-type hypersensitivity responses because these are mediated by CD4 T cells. They had high IgG levels because CD4 T cells help B cell maturation and antibody production, while CD8 T cells suppress these responses, and Tatiana and Alexander were deficient in CD8 T cells. Patients with TAP1/TAP2 deficiencies would have a similar clinical course as Tatiana
Alexander decreased despite normal levels of CD4 T cells?
The intrathymic maturation of CD8 T cells depends on the expression of MHC class I molecules on thymic epithelial cells. Conversely, maturation as CD4 T cells requires interactions with the MHC class II molecules also present on thymic epithelium. Because Tatiana and Alexander do not lack MHC class II molecules, their CD4 T cells are normal and they have normal humoral immunity. When the T-cell antigen receptors on their CD8 T cells were examined, it turned out that they were all : receptors and none were : receptors. How do you explain this? The maturation of CD8 T cells bearing : chains occurs after these cells emigrate from the thymus and is independent of MHC class I expression, whereas the maturation of : CD8 T cells occurs in the thymus and is dependent on the expression of MHC class I molecules. Tatiana and Alexander had normal delayed-type hypersensitivity responses to tuberculin and Candida. Is this surprising in view of their deficiency in CD8 T cells? No. Delayed-type hypersensitivity reactions are provoked by antigen-specific CD4 T cells (see Case 8). Why did Tatiana and Alexander have high levels of serum IgG? The factors that help B cells to mature and secrete immunoglobulins are derived from activated CD4 T cells. These cells were normal in Tatiana and Alexander. Factors that suppress B-cell responses are secreted by CD8 T cells, of which the children had very few. They were therefore not very efficient at terminating B cell-mediated humoral immune reactions and tended to overproduce antibody. In Case 8, we saw the opposite phenomenon in patients with MHC class II deficiency, who have a
deficiency of CD4 T cells and very low levels of serum
immunoglobulins. Genetic defects have also been found in the genes encoding TAP1 and TAPBP. Do you think that the clinical course in these patients would differ from that observed in Tatiana and Alexander? The patients with TAP1 deficiency clinically resembled those with TAP2 deficiency.