A comparison of the lymphoproliferative capacity of pokeweed mitogen (PWM) and phytohaemagglutinin (PHA) in CCR-5 wild-type and heterozygous HIV-infected and uninfected subjects.
Effect of CCR-5 delta 32 heterozygosity in immunological protection was studied by a lymphocyte proliferation assay. Twenty of 86 HIV+ and eight of 32 healthy subjects showed heterozygous mutation (wt/mut) of the CCR-5 gene. Lymphocyte proliferation to pokeweed mitogen was found significantly higher (P < 0.005) in wt/mut versus wild type homozygous (wt/wt) HIV+ subjects in groups with CD4 > 500 and CD4 < 200 cell/ micro L. Phytohaemagglutinin induced stronger proliferation of cells from wt/mut HIV+ subjects with CD4 < 200 cell/ micro L (P = 0.03). Decline of lymphocyte response was more significant among wt/wt groups with different CD4+ cell counts than that between wt/mut groups to both mitogens. Reduced number of CCR-5 receptors on CD4+ cells may decrease the ability of HIV-1 envelope glycoproteins to transduce intracellular signals through CCR-5. Mutation in CCR-5 gene seems to have a benefit in preventing T-cells from HIV envelope-mediated immunopathogenic effects and maintain a relatively normal response to lectins.
Barabás
E
E
National Institute of Dermato-Venereology, Budapest, Hungary. Bareva@bor.sote.hu
Kemény
B
B
González
R
R
Várkonyi
V
V
Nagy
K
K
Horváth
A
A
D000328:Adult; D000704:Analysis of Variance; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D018450:Disease Progression; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D017353:Gene Deletion; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010835:Phytohemagglutinins / Q000627:therapeutic use*; D011043:Pokeweed Mitogens / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D013223:Statistics as Topic / Q000379:methods
D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D019713:Receptors, CCR5