Separate thymus dependent and thymus independent antibody forming cell precursors.
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A 41-residue peptide (HGA-2) containing a continuous sequence of 35 glutamic and aspartic residues was isolated from non-histone chromosomal protein HMG 2. This highly acidic peptide is compared with a similar peptide (HGA-1) isolated from non-histone chromosomal protein HMG 1.
DNA synthesis of normal rat spleen cells in response to endotoxin increases markedly if adherent cells are first removed from the cell suspension. Addition of small numbers of purified macrophages to the cultures restores the response to a low level. T-deprived cells show these effects in very much lesser degree. Large numbers of macrophages completely suppress the response of both normal and T-deprived spleen. We conclude that two mechanisms of suppression are at work: a direct effect of macrophages and a macrophage-dependent "suppressor T cell" effect.
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OBJECTIVE AND BACKGROUND: The aim of the present article is to discuss the potential of gene therapy for thymic hormones as a novel therapeutic strategy to treat dyshomeostatic states associated with athymia, as Di George syndrome, or hypothymic conditions like those associated with AIDS, chronic stress or aging. First we review the advantages of the athymic (nude) mouse as an animal model to implement experimental thymic hormone gene therapy strategies to restore endocrine thymic function. The aging rat, known to be markedly hypothymic, is also considered as an alternative model. METHODS AND EXPECTED RESULTS: The possibility of constructing adenoviral vectors harboring a synthetic gene for the thymic hormone thymulin is discussed. The adenoviral vector so constructed would then be injected intramuscularly in nude mice or senile rats. Transduced myocytes should then begin to act as an ectopic source of thymulin thus restoring circulating thymulin levels to normal youthful levels. CONCLUSION: We conclude that the implementation of thymulin gene therapy should provide novel biotechnological tools that will boost basic studies on the molecular biology of thymulin and would also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models.
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