title: Defective T-lymphocyte chemotactic factor production in patients with established malignancy.
abstract: Lymphocytes from 22 patients with established malignancy were stimulated with concanavalin A (Con A), and supernatants were tested for T-lymphocyte chemotactic factor (LCF). LCF activity was measured using a leading front chemotaxis assay with normal human T cells as responders. Fifteen of the 22 patients tested produced LCF at a level of less than 2 standard deviation below the mean of control cells. In 10 patients where mononuclear cells were stimulated with Con A for 24, 48, and 72 hr, LCF activity was significantly reduced at all three time points averaging 38, 14, and 43% of control levels, respectively. In 13 of the 31 patients, patient T-cell migration in response to casein was measured and compared to the production of LCF by mononuclear cells from these same patients. A significant correlation was observed indicating that both the response of T cells to a migration stimulus, and the production of T-cell-derived LCF was comparably suppressed. The reduction in LCF production by mononuclear cells from patients with established malignancy was not reversed by the addition of indomethacin to the culture system during Con A stimulation indicating that inhibition was not mediated by excessive prostaglandin production. The addition of patient mononuclear cells or T cells to normal mononuclear cells resulted in the inhibition of normal cell LCF by patient mononuclear cells or T cells. This could not be attributed to the production of a lymphocyte chemotactic inhibitor by patient cells, but appeared instead to be due to the direct inhibition of normal cell LCF synthesis or release by patient mononuclear cells or T cells. Separation of patient T cells into Leu 2 suppressor/cytotoxic or Leu 3 helper/inducer T cells showed that the inhibitory activity was associated with the Leu-2 T-cell subset. Heterologous normal Leu 2 T cells did not suppress normal mononuclear cell LCF production suggesting that patient Leu 2 T cells were functionally activated as compared to normal Leu 2 cells. The decreased production of LCF coupled with a depressed T-cell migratory activity in patients with established malignancy may in part be responsible for suppressed cellular immune reactions in these patients and possibly the impairment of tumor rejection.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002469:Cell Separation; D002630:Chemotactic Factors / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D002630:Chemotactic Factors; D003208:Concanavalin A