Proliferative response of mononuclear cells from HIV-infected patients to B-cell mitogens: effects of lymphocyte subset frequency, T-cell defects and prostaglandins.
Proliferative responses of mononuclear cells from patients seropositive for human immunodeficiency virus to B-cell mitogens are severely depressed compared with those of controls. The role of several immunoregulatory phenomena was analyzed. Experimental results show that addition of exogenous lymphokines to cultures increases responses to anti-mu and SAC. Addition of indomethacin to cultures greatly increases the SAC response and causes a smaller increase in the pokeweed mitogen (PWM) response. When both exogenous lymphokines and indomethacin are present in cultures, responses of patients' cells to all three mitogens are positively correlated with the percentage of CD4+ T cells and negatively correlated with the percentage of CD8+ T cells. Responses to anti-mu and SAC are also positively correlated with the percentage of B cells in these cultures. On the basis of these correlations between B-cell responses and lymphocyte subset frequency, patients' B-cell responses can be mathematically corrected to estimate the responsiveness of the B cells in the presence of normal numbers of CD4+ and CD8+ cells. These corrected responses for all three mitogens are virtually identical to control responses. Furthermore, responses of enriched B-cell populations from HIV+ subjects and normal controls to SAC were not significantly different when assays were performed in the presence of indomethacin and exogenous lymphokines. These results suggest that B cells from HIV+ patients are inherently normal in their responsiveness to B-cell mitogens. The depressed function is imposed upon them as a result of the abnormal frequency of lymphocyte subsets in the blood, by increased prostaglandin production, and deficient lymphokine production.
Edelman
A S
AS
Department of Pathology, New York University Medical Center 10016.
Zolla-Pazner
S
S
D001402:B-Lymphocytes / Q000276:immunology*; D006133:Growth Substances / Q000494:pharmacology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000302:isolation & purification / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D013205:Staphylococcal Protein A / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D006133:Growth Substances; D008934:Mitogens; D011453:Prostaglandins; D013205:Staphylococcal Protein A; D007213:Indomethacin