T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics.
The proliferation and cytokine profiles of peripheral blood mononuclear cells (PBMC) from microfilaraemic (Mf+) subjects infected by Loa loa in response to antigens of several parasitic stages were compared with those from amicrofilaraemic (Mf-) individuals. While a strong lymphoproliferative response and consistent levels of both Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-4, IL-5) type cytokines were observed in response to adult worm (AW) and microfilariae (Mf) antigen in Mf- individuals, Mf+ subjects were characterized by a T cell unresponsiveness, including proliferation, cytokine production and IL-2 mRNA expression. Conversely, T cell responsiveness to mitogens and non-specific antigen were similar in the two endemic populations. Depletion of lymphocyte subpopulations indicated that T CD4+ were mainly involved in the specific cellular response. In contrast to other cytokines, IL-10 was produced in response to all parasitic stages, in both Mf+ and Mf- patients. Neutralization of IL-10 did not restore cytokine production in Mf+ patients, while B7 mRNA expression was similar between Mf+ and Mf- subjects in response to Mf antigen, suggesting that IL-10 was not the only factor responsible for T cell unresponsiveness. Mf+ patients have lower Mf antigen-specific IgG levels compared with Mf-, and there is a significant correlation between Mf antigen-specific antibodies and IL-5 responses. These findings suggest that Mf- status is correlated with T helper responsiveness, including proliferation and production of both Th1- and Th2-type cytokines, whereas Mf+ status is characterized by unresponsiveness of the same cell population, induced and/or maintained by microfilariae.
Baize
S
S
Centre International de Recherches Médicales de Franceville (CIRMF), Gabon.
Wahl
G
G
Soboslay
P T
PT
Egwang
T G
TG
Georges
A J
AJ
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000918:Antibody Specificity; D000947:Antigens, Helminth / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology*; D016207:Cytokines / Q000096:biosynthesis*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008117:Loa / Q000254:growth & development / Q000276:immunology*; D008118:Loiasis / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D000939:Epitopes; D007074:Immunoglobulin G; D015848:Interleukin-5; D012333:RNA, Messenger; D016753:Interleukin-10