Cancer and immunity: the progress, the disappointments, the lessons of both. I. Antigenicity.
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Biomedical subjects
Publications and source records attributed to R A Good.
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We investigated suppressor and helper T cells in 19 patients with variable immunodeficiency to assess the possibility that defective interactions among these cells and B lymphocytes are the chief cause of the inadequate plasma-cell development and hypogammaglobulinemia characterizing these syndromes. We accomplished functional separation of the two T-cell subsets, using irradiation, which selectively inactivates T-cell suppressors. The patient B lymphocytes were usually capable of some differentiation into plasma cells when co-cultured with T cells manipulated to optimize helper effects. Eighteen of 19 patients showed quantitatively poor plasma-cell production even under these conditions. However, only one had defective enough helper function, and only one sufficiently excessive suppressor activity for these factors to be considered the major pathogenetic process in each case. Since neither an absolute defect in B cells nor consistent abnormalities in modulator T cells were demonstrable in most patients, other explanations must be sought for the mechanisms underlying this form of primary immune deficiency.
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Peripheral blood from 16 patients with mycosis fungoides and two patients with Sézary syndrome was examined for T, B, and third-population (K) cells, using a battery of surface markers. T lymphocytes as determined by spontaneous rosette formation with sheep erythrocytes and third-population cells as determined by the Ripley rosette test were present in normal proportions. Surprisingly, B lymphocytes, as determined by surface immunoglobulin and receptors for mouse erythrocytes, were either lacking or were present in low proportions in some patients. Normal proportions were present in others. Repeat studies of two of three patients lacking B lymphocytes, following treatment, revealed normal or low proportions of B cells. Two patients with mycosis fungoides had increased proportions of "null" cells. Study of lymphoid cell subpopulations before and after leukopheresis in a single patient demonstrated a decrease in T cell proportions associated with a concomitant increase in the proportions of "null" cells following this therapy.
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In the indirect assay for leukocyte migration inhibitory factor (LIF), lymphokine-rich supernatants were obtained by culture of stimulated lymphocytes and then tested for LIF activity in agarose plates using purified granulocytes as target cells. Studies on the standardization of the conditions under which LIF acts on the target cells are described, with emphasis on the use of "standard" supernatants of known LIF activity and the influence of pH on the action of LIF and the sensitivity of the assay. The observation that LIF activity is reduced when the ambient pH falls below 7.2 is suggested as an explanation firstly for the "escape" phenomenon seen particularly in capillary tube assays for LIF, and secondly for the reduced sensitivity of the capillarly tube assay in comparison with the corresponding agarose plate assay.
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