T‐cell analysis in identical twins reveals an impaired anti‐follicular lymphoma immune response in the patient but not in the healthy twin

E Gitelson, D Spaner, R Buckstein… - British journal of …, 2002 - Wiley Online Library
E Gitelson, D Spaner, R Buckstein, E Franssen, K Hewitt, MS Lim, N Pennell, JL Schultze
British journal of haematology, 2002Wiley Online Library
In lymphomas an innate defect in the T‐cell repertoire could account for the impaired tumour‐
specific immune response; alternatively, the tumour itself could exert an inhibitory effect on
the immune system. To address this issue we analysed the T‐cell responses against
follicular lymphoma (FL) in identical twins as it can be postulated that their overall T‐cell
repertoire is identical. While differences between the T‐cell response of the patient and the
healthy twin would point to a tumour‐induced T‐cell unresponsiveness, impaired responses …
Summary
In lymphomas an innate defect in the T‐cell repertoire could account for the impaired tumour‐specific immune response; alternatively, the tumour itself could exert an inhibitory effect on the immune system. To address this issue we analysed the T‐cell responses against follicular lymphoma (FL) in identical twins as it can be postulated that their overall T‐cell repertoire is identical. While differences between the T‐cell response of the patient and the healthy twin would point to a tumour‐induced T‐cell unresponsiveness, impaired responses in both would point to a defective T‐cell repertoire. We demonstrated an impaired tumour‐specific proliferation (P = 0·035 and P = 0·013) and cytokine release (P = 0·004 and P = 0·0008) of both peripheral blood and tumour‐derived T‐cells, respectively, in the FL patient compared with the T‐cell response of the healthy twin. Moreover, only syngeneic primed T cells were able to directly lyse unmodified FL cells of the patient. These data support previous findings in murine lymphomas and suggest that inhibitory mechanisms during tumour growth, rather than a defective T‐cell repertoire, are responsible for the insufficient T‐cell response in lymphoma.
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