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Phosphocholine-Containing Antigens of Brugia Malayi Nonspecifically Suppress Lymphocyte Function

Renu B. LalNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Tuberculosis Research Center, Bethesda, Maryland, India

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V. KumaraswamiNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Tuberculosis Research Center, Bethesda, Maryland, India

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Cathy SteelNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Tuberculosis Research Center, Bethesda, Maryland, India

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Thomas B. NutmanNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Tuberculosis Research Center, Bethesda, Maryland, India

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The immunosuppressive effect of Brugia malayi antigen (BmA) on phytohemagglutinin (PHA) driven T cell proliferation was evaluated in patients with filariasis (n = 14) and compared to control individuals (n = 12). When peripheral blood lymphocytes were co-cultured with BmA and PHA, BmA markedly suppressed the T cell proliferative response to PHA in both filarial patients and control individuals in a dose-dependent manner. The suppression resulted neither from any direct toxicity of BmA nor from non-specific absorption of the PHA mitogenic activity by BmA. The major suppressive component appears to be phosphocholine (PC), an immunodominant molecule present in abundance on filarial parasites and on circulating filarial antigen. Both purified PC as well as PC-containing antigens affinity purified from BmA were capable of suppressing the proliferative responses of co-cultured autologous lymphocytes to PHA. The suppressive activity was not abolished by mitomycin-C treatment and was greater in patients with filariasis than in normal controls, suggesting that levels of PC-containing antigens determines the magnitude of the suppressive effect of PC-antigen. Further, as induction of the suppressive activity was completely abrogated when antigen pre-treated cells were T cell-depleted, the suppressive effect appears to be mediated primarily by T cells.

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