Cytokine control of parasite-specific anergy in human lymphatic filariasis : Preferential induration of a regulatory T helper type 2 lymphocyte subset.

Christopher King, L.; Siddhartha Mahanty; Kumaraswami, V.; John Abrahams, S.; Jaya Regunathan; Kunthala Jayaraman; Ottesen Eric, A.; Thomas Nutman, B.

Journal of Clinical Investigation; 1993; 92; 1667-1673.

The immunological mechanisms involved in maintenance of an asymptomatic microfilaremic state (MF) in patients with lymphatic filalriasis remain undefined. MF patients have impaired filarial antigen (Ag)-specific lymphocyte proliferation and decreased frequencies (Fo) of Ag-specific T cells, and yet elevated serum IgE and antifilarial IgG4. To investigate the mechanism of Ag-specific anergy in MF patients in contrast to amicrofilaremic individuals with chronic lymphatic obstruction (CP), the Fo of Ag-specific lymphocytes from peripheral blood mononuclear cells secreting either IL-4 or IFN- g were assessed by filter spot enzyme-linked immunosorbent assay, and IL-10 and transforming growth factor-b (TGF- b ) mRNA transcript levels were assessed by a semiquantitative reverse transcriptase polymerase chain reaction technique. The Fo of filaria-specific IL-4 secreting lymphocytes were equivalent in both MF (geometric mean(GM) = 1:11,700) and CP (GM = 1:29,300p=0.08), whereas the Fo of IFN- g -secreting lymphocytes were lower in MF (GM = 1:39,300) than in CP (GM = 1:4,200, p < 0.01). When the ratio of IL-4/IFN-g (T helper type 2 (Th2/TH1)-secreting cells was examined, MF subjects showed a predominant Th2 response (8:1) compared with a Th1 response in CP individuals (1:4). mRNA transcript levels of IL-10 were also significantly elevated in MF compared with CP individuals (P < 0.01). Further, IL-10 and TGF- b were shown to have a role in modulating the Ag-specific anergy among MF subjects, in that neutralizing anti-IL-10 or anti-TFG- b significantly enhanced lymphocyte proliferation response (by 220-1,300%) to filarial Ags in MF individuals. These findings demonstrate that MF subjects respond to parasite antigen by producing a set of suppressive cytokines that may a facilitate persistence of the parasite within humans while producing little clinical disease.

Back to List of publications / Home