Defective helper function of purified T4 cells and excessive suppressor activity of purified T8 cells in patients with B-cell chronic lymphocytic leukemia. T4 suppressor effector cells are present in certain patients.
We investigated helper and suppressor functions to B-cell responses and T-T cell interactions of purified T4 and T8 cells from 20 untreated patients with B-cell chronic lymphocytic leukemia (CLL). Appropriate mixtures of purified T4 or T8 cells from patients with CLL were cultured with purified B cells or T4 and B cells from normal donors for 7 days with pokeweed mitogen (PWM). IgM, IgA, and IgG produced were determined in the supernatants of these cultures by a heavy chain-specific enzyme-linked immunosorbent assay (ELISA) and compared to those obtained by the corresponding mixtures of T4, T8, and B cells from normal donors. Purified T4 cells from 14 of 20 patients with CLL exhibited defective helper function (P less than .001) to immunoglobulin (Ig) production by purified B cells from normal donors. Purified T4 cells from 6 of these 14 patients were able to suppress significantly (P less than .001) and in a concentration-dependent manner Ig production by mixtures of T4 and B cells from normal donors, in the absence of T8 cells. These suppressor effector T4 cells from certain patients were partially radiosensitive. Purified T8 cells from 8 of 20 patients with CLL exhibited excessive suppressor activity. These cells significantly suppressed (P less than .001), Ig production by mixtures of T4 and B cells from normal donors to a degree significantly higher (P less than .005) than that observed by equal numbers of T8 cells from normal donors. This inhibition was dependent on the numbers of the T8 CLL cells added to the cultures. Excessive suppressor activity by T8 CLL cells was at least in part radiosensitive in four of eight patients. These results demonstrate a wide range of immunoregulatory T-cell abnormalities in patients with CLL. Naturally occurring T4 suppressor effector cells, directly inhibiting Ig production by mixtures of T4 and B cells, in the absence of T8 cells, are present in certain patients with CLL.
Kunicka
J E
JE
Memorial Sloan-Kettering Cancer Center, New York.
Platsoucas
C D
CD
D000917:Antibody Formation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007945:Leukemia, Lymphoid / Q000503:physiopathology*; D008211:Lymphocyte Cooperation; D011043:Pokeweed Mitogens / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology* / Q000528:radiation effects
D000945:Antigens, Differentiation, T-Lymphocyte; D011043:Pokeweed Mitogens