T cell responses in aplastic anemia

Immunosuppressive drugs generally lead to substantially improved blood cell counts in individuals with aplastic anemia (AA), a severe decline of all blood cell lineages in which the marrow is deficient in hematopoietic cells. For this reason, although AA’s pathogenesis is obscure, it seems likely that autoimmune responses block hematopoiesis at an early stage but do not entirely eliminate early pluripotent stem cells. Here, Zeng and coworkers provide a first glimpse at some quirks of the immune system in AA patients. These authors have prepared T cells from within the marrow of 5 people with serious but treatable aplastic anemia. Cloning and DNA analysis of the T cell receptors from one of these patients shows that one sequence form of the complementarity determining region CDR3 is highly represented in patients’ marrow. This form, dubbed JZ1.1, carries a specific heptapeptide sequence that is also found in the other patients studied but is absent in controls. Isolated T cells of this TCR type can suppress hematopoietic stem cell proliferation in co-culture experiments, diminishing the growth of myeloid and erythroid cell precursors alike. Interestingly, these JZ1.1 T cells appear to be specific for autologous stem cells derived from the patient at a time of severe disease– marrow cells derived from a healthy, MHC-matched control donor, or even from the patient after successful treatment, are not killed by exposure to JZ1.1 cells. Hence, it appears that T cells of this type are activated to respond to some still-unknown determinant that is present on early hematopoietic stem cells during periods of acute disease.

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