Historical background

Until the early 1960s small lymphocytes were regarded as short-lived resting cells of obscure function. In 1962 Gowans and his colleagues observed that purified small lymphocytes transferred from thoracic duct lymph of rats were able to transform into blast cells when injected into irradiated mice. This experiment provided the first unequivocal evidence that small lymphocytes were capable of being triggered to enter cell cycle. Two years later, independent studies by Bain and colleagues and by Bach and Hirschorn demonstrated that a mixture of blood leukocytes taken from two unrelated donors generated large numbers of blast lymphoid cells after several days in tissue culture. Bain and colleagues made the critical discovery that blast transformation failed to occur between cells from monozygotic twins. Shortly afterwards other workers demonstrated that the mixed leukocyte reaction (MLR) was demonstrable in a number of different species and that the strongest reactions occurred with disparity at the major histocompatibility complex (MHC), i.e. the HLA complex in man and the H-2 complex in mice. With the discovery that small lymphocytes were divisible into thymus-derived (T) and bone marrow-derived (B) cells, the MLR was shown to reflect the proliferative response of T cells, with few or no B cells involved as responding cells.

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