ABSTRACT
Forkhead box protein 3 (FoxP3)(+) regulatory T cells (Tregs ) are important not only in regulating the development of autoimmune conditions, but also in chronic infectious diseases. Given their cardinal function in suppressing immune activation, research has focused upon whether they play a detrimental role in chronic infections, particularly HIV. While the role of Tregs in HIV has been investigated intensively, it remains an unresolved topic. However, it is generally accepted that Tregs are susceptible to HIV infection and are preferentially preserved over conventional CD4(+) T cells. It is unknown whether the peripheral-induced or the thymic-derived Tregs are more susceptible to HIV cytotoxicity. It has been recognized that Tregs can be segregated into two subsets based on Helios expression, with the vast majority being Helios(+) . This study examines the impact of HIV infection on total Tregs and their Helios subsets in a perinatal-acquired HIV-infected paediatric population. The finding indicates a selective expansion or survival of Tregs in association with CD4 depletion and increased viraemia. The Helios(+) and Helios(-) subsets within Tregs appear to be equally affected. However, the Helios(+) Tregs seem to be more preserved in patients with low CD4(+) ≤ 25% and detectable plasma HIV RNA >20 copies/ml. In this group, the frequencies of Tregs are increased, but their numbers appear insufficient to restrain immune activation. In conclusion, our findings suggest that both Helios subsets of Tregs are susceptible to HIV infection and are preferentially preserved compared to conventional CD4(+) T cells.
Subject(s)
Forkhead Transcription Factors/immunology , Gene Expression Regulation/immunology , HIV Infections/immunology , HIV-1/immunology , Ikaros Transcription Factor/immunology , T-Lymphocytes, Regulatory/immunology , Adolescent , Adult , Child , Child, Preschool , Chronic Disease , Female , Forkhead Transcription Factors/biosynthesis , HIV Infections/blood , HIV Infections/congenital , HIV Infections/pathology , HIV-1/metabolism , Humans , Ikaros Transcription Factor/biosynthesis , Infant , Male , RNA, Viral/blood , RNA, Viral/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathology , Thymus Gland/immunology , Thymus Gland/metabolism , Thymus Gland/pathologyABSTRACT
Susceptibility of the snail Biomphalaria glabrata to infection with the digenetic trematode Echinostoma paraensei was correlated with the ability of secretory-excretory products (SEP) derived from sporocysts of this parasite to interfere with the spreading behavior of host hemocytes in an in vitro assay. In 15 separate experiments, the prevalence of infection achieved by miracidia was positively correlated (C.C. = 0.779, P < 0.001) with the ability of in vitro-transformed sporocysts derived from the same batches of miracidia to produce SEP that inhibited host hemocyte spreading. Under assay conditions reflecting differences in hemolymph volumes between juvenile snails (susceptible to infection) and adult snails (relatively refractory to infection), SEP had a significantly greater effect on hemocytes from juvenile snails. No significant differences in response to SEP were noted when equivalent numbers of adult and juvenile hemocytes were used in the assay. Snails of the M line strain of B. glabrata are significantly more susceptible to infection with E. paraensei than 13-16-R1 strain snails. Exposure to SEP significantly increased the number of unspread hemocytes for both strains. However, significantly more 13-16-R1 than M line hemocytes remained spread following SEP treatment. Echinostoma paraensei sporocyst SEP effects on host hemocyte spreading mirror observed patterns in both age- and strain-related susceptibility of B. glabrata to this parasite. The results suggest that the number of hemocytes available to a particular snail influences its vulnerability to infection with E. paraensei.
