Nitric oxide limits the expansion of antigen-specific T cells in mice infected with the microfilariae of Brugia pahangi.
Infection of BALB/c mice with the microfilariae (Mf) of the filarial nematode Brugia pahangi results in an antigen-specific proliferative defect that is induced by high levels of NO. Using carboxyfluorescein diacetate succinimydl ester and cell surface labeling, it was possible to identify a population of antigen-specific T cells from Mf-infected BALB/c mice that expressed particularly high levels of CD4 (CD4(hi)). These cells proliferated in culture only when inducible NO synthase was inhibited and accounted for almost all of the antigen-specific proliferative response under those conditions. CD4(hi) cells also expressed high levels of CD44, consistent with their status as activated T cells. A similar population of CD4(hi) cells was observed in cultures from Mf-infected gamma interferon receptor knockout (IFN-gammaR(-/-)) mice. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining revealed that the CD4(+) T cells from Mf-infected wild-type mice were preferentially susceptible to apoptosis compared to CD4(+) T cells from IFN-gammaR(-/-) mice. These studies suggest that the expansion of antigen-specific T cells in Mf-infected mice is limited by NO.
O'Connor
Richard A
RA
Department of Veterinary Parasitology, University of Glasgow, Glasgow G61 1QH, Scotland.
Devaney
Eileen
E
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D017209:Apoptosis; D017179:Brugia pahangi / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D005368:Filariasis / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008842:Microfilariae / Q000276:immunology*; D009569:Nitric Oxide / Q000502:physiology*; D017471:Receptors, Interferon / Q000502:physiology; D019014:fas Receptor / Q000096:biosynthesis; D000096743:Interferon gamma Receptor
D000947:Antigens, Helminth; D018960:Hyaluronan Receptors; D007371:Interferon-gamma; D009569:Nitric Oxide; D017471:Receptors, Interferon; D019014:fas Receptor; D000096743:Interferon gamma Receptor