Stabilization and characterization of antigen-specific T suppressor inducer and T suppressor effector molecules

Malley, Arthur; Zeleny-Pooley, Michelle; Murray, Geraldine

doi:10.1016/0022-1759(94)00237-q

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…Soluble suppressive substances which have been de scribed in other systems include T cell receptor molecules [1,2,12] and cytokines, notably interleukins 2, 4 and 10, y-interferon and transforming growth factor [5 [1,2,12,[52][53][54], Some investigators have hypothesized, in fact, that poorly defined suppressor factors reported previously were actually cytokines which had not yet been described when the suppressive phenomena were originally discovered [55, 56], CosynthesisofThl-like and Th2-like cytokines may be a characteristic of antigen-specific Ts cells as well [57]. We are currently investigating the role of cytokines in MANspecific suppression.…”

Section: Discussionmentioning

confidence: 99%

Candida albicans Mannan-Specific, Delayed Hypersensitivity Down-Regulatory CD8+ Cells Are Genetically Restricted Effectors and Their Production Requires CD4 and l-A Expression

S²,

Wang³

et al. 1996

Int Arch Allergy Immunol

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There is considerable controversy over the induction and activity of down-regulatory cells active in various antigen-specific and antigen-nonspecific systems. We have been studying the nature of such cells in a Candida albicans mannan (MAN)-specifιc system for some time and report here the requirements for CD4+ and I-A+ cells during the inductive phase for the development of CD8+ effector cells, as well as the requirement for genetic compatibility for effector activity of CD8+ cells. Since we have shown previously that CD8+ down-regulatory cells were present in spleens of MAN-treated mice 4 days following the administration of MAN to naive mice, as determined by their ability to suppress delayed hypersensitivity (DH) when transferred to immunized recipients, we treated mice with monoclonal antibodies specific for CD4 and I-A at various times before, with or after the administration of MAN to assess the role of CD4+ and I-A+ cells in the development of the CD8+ effector cell. Both anti-CD4 and anti-I-A given before or up to 30 h after the administration of MAN abrogated the ability of splenocytes from MAN-treated mice to down-regulate MAN-specific DH in immunized recipients. Moreover, transfers of down-regulatory cells between H-2-incompatible strains of mice, specifically CBA/J and BALB/cByJ, provided evidence that the effector cell for the down-regulatory activity was also restricted genetically in its activity. Taken together, the data presented indicate that genetically compatible cells are required for both the inductive and effector stages of down-regulation of MAN-specific DH, suggesting that cell-cell cooperation is required for both stages and that CD4+ cells are required in a pathway leading to the development of the CD8+ effector cell.

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Section: Discussionmentioning

confidence: 99%

Candida albicans Mannan-Specific, Delayed Hypersensitivity Down-Regulatory CD8+ Cells Are Genetically Restricted Effectors and Their Production Requires CD4 and l-A Expression

S²,

Wang³

et al. 1996

Int Arch Allergy Immunol

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“…Despite the debate, there is no question that the phenomenon occurs; it has been demonstrated in fungal models by us (8,18) and others (5,13,16,32,49), in bacterial and parasitic systems (reviewed in reference 68), and in systems involving CS (reviewed in reference 1). There has been something of a renewed interest in suppressive phenomena; IL-10 production by autoreactive CD8 ϩ T-cell clones has been described (31), and IL-10 epitopes (43) have been associated with antigen-specific T suppressor cells. Moreover, Nanda et al (50) have described a unique pattern of lymphokine synthesis involving the cosynthesis of IL-10 and IFN-␥ in selected antigen-specific suppressor T-cell clones.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Involvement in Immunomodulatory Activity Affected byCandida albicansMannan

Wang

Moser

et al. 1998

Infect Immun

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Candida albicans mannoprotein (MAN) administered intravenously to mice stimulates the production of splenic CD8+ effector cells which downregulate delayed hypersensitivity (DH) in immunized mice. Cytokine involvement in the induction and/or elicitation of downregulation was studied by (i) examining murine splenocytes qualitatively for mRNA for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, and gamma interferon (IFN-γ), (ii) quantitating splenocyte mRNA for IL-12p40 by quantitative-competitive reverse transcriptase-mediated PCR, and (iii) measuring serum levels of IL-12p40 and IL-12p70 by capture enzyme-linked immunosorbent assay, each performed at selected intervals over 96 h after giving MAN. Further, the effect of in vivo administration of anti-IL-4 on the induction and elicitation of MAN-specific DH in MAN-treated mice was measured. Expression of IL-12p40 mRNA in the spleen was reduced to near 0 during the first 24 h but rebounded thereafter. Transcripts for IL-10 were present throughout the 96-h period, whereas those for IL-4 and IFN-γ were either weak or undetectable prior to 24 to 48 h. In vivo administration of anti-IL-4 partially abrogated the downregulatory effect of MAN only when given at the time of MAN administration. Serum levels of IL-12p40, but not IL-12p70, were increased by 24 h and maximal at 48 h. The antagonistic effect of IL-12p40 could contribute to the mechanism(s) for downregulation of DH. Moreover, IL-10, IL-4, and/or IFN-γ, interacting with MAN-activated cells in the absence of biologically active IL-12, may induce the production of CD8+ downregulatory effector cells. Partial abrogation of downregulatory activity in animals treated with anti-IL-4 at the time of induction of such activity lends support to this hypothesis.

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“…Extracellular, T‐cell–derived proteins that bind specifically to nominal (non‐MHC‐associated) antigen have been described in T‐cell culture fluids (1–11) and murine (12–14), and human (15, 16) serum. These immunoproteins bear T‐cell receptor (TCR variable region (15) and α chain constant region (8, 10, 17, 18) epitopes.…”

mentioning

confidence: 99%

“…Soluble, antigen‐specific T‐cell–derived immunoregulatory factors (7) and TABM share epitopes (10) and are physically and functionally associated with immunoregulatory cytokines (10, 21). We have suggested that TABM may function by antigen‐specific focusing of immunoregulatory cytokines such as IL‐10 and TGF‐β to an area where antigen is deposited (10, 11, 16).…”

mentioning

confidence: 99%

Detection of Antigen‐Specific Human Serum Proteins Related to the T‐Cell Receptor in Infectious Disease and in an Immune Response to Milk Proteins or Chemicals

Little¹,

Georgiou

Fey

et al. 2000

Proc Soc Exp Biol Med

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Abstract. A monoclonal IgG2 antibody, MG3C9–1 A12, was prepared by immunization of mice with human serum Cohn Fraction III proteins enriched for TCR Ca+ proteins. MG3C9–1 A12 bound to Mr 28,000, antigen‐specific TCR Ca+, β−, and TCR Ca+, β+ serum proteins associated with TGF‐β1, 2. The IgG2 monoclonal antibody also bound to T‐lymphocyte proteins but did not bind to B lymphocyte proteins, human albumin, IgM, IgG, IgA, or TGF‐β1, 2, 3 immunogenic peptides. Monoclonal MG3C9–1 A12 detected TCR‐related proteins specific for filarial extract, milk proteins, or benzoic acid in the sera of individuals with chronic or asymptomatic filariasis, milk intolerance, or sensitivity to toluene, respectively. TCR‐related serum proteins were also detected intracellularly in mononuclear cells in frozen sections of ileum from a patient with milk intolerance and reactive mesenteric lymph nodes from a patient with a gastric ulcer. The results suggest that antigen‐specific TCR‐related serum proteins may be elevated during an immune response to oral, environmental, or infectious stimuli.

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Stabilization and characterization of antigen-specific T suppressor inducer and T suppressor effector molecules

Cited by 7 publications

References 23 publications

<i>Candida albican</i><i>s</i> Mannan-Specific, Delayed Hypersensitivity Down-Regulatory CD8+ Cells Are Genetically Restricted Effectors and Their Production Requires CD4 and l-A Expression

<i>Candida albican</i><i>s</i> Mannan-Specific, Delayed Hypersensitivity Down-Regulatory CD8+ Cells Are Genetically Restricted Effectors and Their Production Requires CD4 and l-A Expression

Cytokine Involvement in Immunomodulatory Activity Affected byCandida albicansMannan

Detection of Antigen‐Specific Human Serum Proteins Related to the T‐Cell Receptor in Infectious Disease and in an Immune Response to Milk Proteins or Chemicals

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