Antigen-Specific Suppressor Cells and Suppressor Factors in Human Filariasis with<i>Brugia malayi</i>

Piessens, Willy F.; Ratiwayanto, Sutanti; Tuti, Sekar; Palmieri, James H.; Piessens, P W; Koiman, Iskak; Dennis, David T.

doi:10.1056/nejm198004103021503

Cited by 105 publications

(52 citation statements)

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“…illy (20), and as markedly reduced T lymphocyte proliferation responses to parasite antigens in vitro, but not to nonparasite antigens (4,9,10,21). The specific B cell deficits in these microfilaremic patients are reflected both in low serum levels of parasite-specific antibodies (3,6,22) and in impaired immunoglobulin production by PBMC in response to parasite antigens in vitro (7).…”

Section: Resultsmentioning

confidence: 99%

“…The mechanisms underlying this parasite-specific immune hyporesponsiveness have been postulated to involve adherent suppressor cells (presumably monocytes), serum suppressive factors (9), or suppressor T lymphocytes (10). Alternatively, the immunologically hyporesponsive microfilaremic state may result from a diminished number of parasite antigen-responsive lymphocytes (7) as a consequence of perinatal sensitization or tolerization to the parasite.…”

Section: Introductionmentioning

confidence: 99%

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Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.

et al. 1992

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To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Igproducing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, ISLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean IGMI, 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P < 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P < 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state. (J.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.

et al. 1992

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“…In particular, both down-regulation by IL-10 and/or TGF-␤ (4 -7), regulation by Th3 or Tr1 cells (3), and changes in the balance of type 1 and type 2 CD4 ϩ cells (4,8) have each been implicated as important mechanisms underlying the filaria-specific down-regulated state. Indeed, Ͼ2 decades ago it was demonstrated that patently infected (microfilaria-positive (Mf ϩ ) 2 ) patients had demonstrable Ag-specific suppressor T cells (9) as well as non-T cell-derived suppressor factors (10). More recently, it has been shown that most, but not all, (11) of this modulating activity is a consequence of the interaction between the microfilarial stage of the parasite (12) and the host cellular immune system, some of which may occur neonatally (13-18).…”

Section: Ctla-4 In Filarial Infectionsmentioning

confidence: 99%

CTLA-4 in Filarial Infections: Implications for a Role in Diminished T Cell Reactivity

Steel

Nutman

2003

The Journal of Immunology

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To determine the role that CTLA-4 might play in mediating the diminished parasite Ag-specific T cell responsiveness that is characteristically seen in filaria-infected patients, several study populations and methods were used. First, quantitative assessment of mRNA expression determined that PBMC from uninfected adolescents exposed in utero to microfilarial (Mf) Ag demonstrated a strong up-regulation of CTLA-4 to the Mf stage of the parasite in contrast to that observed in cells from children born of uninfected mothers (p = 0.005). Next, the frequency of CTLA-4 expression was examined using flow cytometry in cells from filaria-infected and -uninfected individuals ex vivo. Individuals born in filarial endemic regions of the world (with long-standing infections) had greater percentages of CD4+CTLA-4+ cells than did expatriate infected or uninfected individuals (p = 0.005 and 0.05, respectively); in addition, Mf+ patients demonstrated higher frequencies of CD4+CTLA-4+ and CD8+CTLA-4+ cells (p = 0.027 and 0.037, respectively) than did Mf− infected individuals. Of interest, the greatest intensity of CTLA-4 expression occurred in CD4+CD25+ cells, a population purported to include suppressor cells. Finally, in vitro blocking of CTLA-4 expression in PBMC from filaria-infected individuals induced a mean increase of 44% in IL-5 production to Mf Ag, whereas there was a concurrent mean decrease of 42% in IFN-γ production, suggesting that CTLA-4 also acts to alter the Th1/Th2 balance in filaria-infected individuals. Together, these data indicate a significant role for CTLA-4 in regulating the host response to filarial infections and that factors such as length of exposure and patency are important codeterminants.

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“…Parasite prod-ucts that suppress in vitro lymphocyte responses to specific antigens have been described in chronic mucocutaneous candidiasis (12), schistosomiasis (1), leprosy (13), and tuberculosis (14). Moreover, autologouis seruim inhibits in vitro responses of lymphocytes from patients with schistosomiasis (15), histoplasmosis (16), filariasis (3), and tuberculosis (17). Our study of tuberculosis explored whether suppressive plasma factors, possibly mycoblacterial in origin, alter monocyte function, and thereby induce immunosuppression during the course of infection.…”

Section: Introductionmentioning

confidence: 99%

Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility.

Kleinhenz¹,

Ellner²,

Spagnuolo³

et al. 1981

J. Clin. Invest.

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A B S T R A C T During tuberculosis, exposure of monocytes to circulating factors may induce the suppressor activity observed in some anergic patients. To explore this possibility, we examined the effects ofplasma pooled from 28 untreated tuberculosis (TB) patients and the mycobacterial cell wall polysaccharide Darabino-D-galactan (AG) on the in vitro function of peripheral blood mononuiclear cells (PBMC) from healthy donors. In the [3H]thymidine incorporation assay, stimuilated responses of PBMC inctubated in culture meditum stupplemented with TB plasmia or co-cultured with 3.0 ,ug/ml AG were depressed significantly when compared with control responses. Cytotoxicity and altered kinetics of stimulated DNA synthesis did not contribute to the observed suppression. TB plasma and AG-induced suppression of the PBMC response to purified protein derivative was monocyte dependent and indomethacin reversible. In addition, TB plasma and AG directly inhibited the phytohemagglutininstimulated responses of T lymphocytes. In a quantitative assay of monocyte attachment to plastic, both TB plasma and AG significantly increased monocyte adherence from basal levels. These effects on monocyte adherence were reversed with indomethacin or antibody to mycobacterial polysaccharide. In addition, TB plasma passed over an immunoabsorbent column of

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Antigen-Specific Suppressor Cells and Suppressor Factors in Human Filariasis withBrugia malayi

Cited by 105 publications

References 8 publications

Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.

Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.

CTLA-4 in Filarial Infections: Implications for a Role in Diminished T Cell Reactivity

Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility.

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