T-suppressor cells

Suppressor T cells. These cells can be specific for the antigen receptors on both B and T cells and thereby can suppress the activity of these two groups of cells. 

Bloom B.R., Salgame P. Diamond B. (1992) Revisiting and revising suppressor T cells. Immunol Today, 13,131-136. 

Immunological abnormalities were reported in 23 adults in Woburn, Massachusetts, who were exposed to contaminated well water and who were family members of children with leukemia (Byers et al. 1988). These immunological abnormalities, tested for 5 years after well closure, included persistent lymphocytosis, increased numbers of T-lymphocytes, and depressed helper suppressor T-cell ratio. Auto-antibodies, particularly anti-nuclear antibodies, were detected in 11 of 23 adults tested. This study is limited by the possible bias in identifying risk factors for immunological abnormalities in a small, nonpopulation-based group identified by leukemia types. Other limitations of this study are described in Section 2.2.2.8. A study of 356 residents of Tucson, Arizona, who were exposed to trichloroethylene (6-500 ppb) and other chemicals in well water drawn from the Santa Cmz aquifer found increased frequencies of 10 systemic lupus erythematosus symptoms, 5 (arthritis, Raynaud s phenomenon, malar rash, skin lesions related to sun exposure, seizure or convulsions) of which were statistically significant (Kilbum and Warshaw 1992). 

Regulatory T cells, or suppressor T cells, suppress the activation of an immune response. The activity of these cells in organ transplant is not well elucidated. 

Byrnes, D. M., M. H. Antoni, K. Goodkin, j. Efantis-Potter, D. Asthana, T. Simon et al., Stressful Events, Pessimism, Natural Killer Cell Cytotoxicity, and Cytotoxic/Suppressor T Cells in Hiv+ Black Women at Riskfor Cervical Cancer , Psychosomatic Medicine 60 (1998) 714-22... 

Shevach, E., CD4+CD25+ suppressor T cells More questions than answers, Nat. Rev. Immunol., 2, 389, 2002. 

Mercuric chloride in the BN rat gives a lymphoproliferation in spleen and lymph nodes, including B and T helper cells, an increase in the number of Ig containing cells resulting in a rise in all serum Ig isotypes and an early thymic atrophy [196]. The kinetics of the increase in the serum level of various Ig isotypes were similar to that observed for IgE, suggesting spontaneous autoregulation, which could involve suppressor T cells [ 197, 198] and/or auto-anti-idiotypic antibodies [ 199]. 

Type IV Delayed-type Hypersensitivity (DTH). Delayed-type hypersensitivity reactions are T-cell mediated with no involvement of antibodies. However, these reactions are controlled through accessory cells, suppressor T cells, and monokine-secreting macrophages, which regulate the proliferation and differentiation of T cells. The most frequent form of DTH manifests itself as contact dermatitis. The drug or metabolite binds to a protein in the skin or the Langerhans cell membrane... 

Type IV hypersensitivity responses are elicited by T lymphocytes and are controlled by accessory cells and suppressor T cells. Macrophages are also involved in that they secrete several monokines, which results in proliferation and differentiation of T cells. Thus, there are numerous points along this intricate pathway in which drugs may modulate the final response. To achieve a Type IV response, an initial high-dose exposure or repeated lower-dose exposures are applied to the skin the antigen is carried from the skin by Langerhans cells and presented to cells in the thymus to initiate T-cell proliferation and sensitization. Once sensitized, a second challenge dose will elicit an inflammatory response. Thus, before sensitivity can be assessed, each of the models used to evaluate dermal hypersensitivity requires as a minimum ... 

Wan YY, Flavell RA Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc Natl Acad Sci USA 2005 102 5126-5131. 

Von Boehmer H Mechanisms of suppression by suppressor T cells. Nat Immunol 2005 6 338-344. 

Shevach EM CD4 4- CD25 + suppressor T cells more questions than answers. Nat Rev Immunol 2002 2 389-400. 

Germain RN A rose by any other name from suppressor T cells to Tregs, approbation to unbridled enthusiasm. Immunology 2008 123 20-27. 

Suppressor T cells were also shown to express a major histocompatibility complex (MHC) class II marker, I-J. However, because I-J was never cloned and its presence in the MHC never shown formally, there was considerable doubt as to the significance of I-J [reviewed in 3, 4]. 

Suppression of the DTH Response The induction and regulation of CD8+ Tregs in vivo is complex and dependent on several cell types [2,3], In vivo, the induction of CD8-I- suppressor T cells required Lyt-l-l- (CD4) suppressor-inducer T cells that did not directly suppress DTH. The mechanism of this induction was not clear but appeared to be mediated by antigen-specific, soluble molecules produced by the suppressor-inducer T cells [18]. Additionally, the in vivo induction of CD8+ suppressor T cells requires cells sensitive to the cytotoxic effects of cyclophosphamide [19,20]. 

The suppression of DTH (in vivo) by CD8-I-Tregs affords a direct demonstration of the suppressive effects of these cells on effector T cells because adoptive transfer assays demonstrate a suppressive effect on the DTH response within 24 h of the introduction of CD8-I- Tregs into the challenge site for DTH at the time of challenge with the antigen. The ability of CD8-I- suppressor T cells to suppress directly DTH in vivo has been measured by the local adoptive transfer assay (LAT) that transfers DTH to naive recipients by... 

T cells could suppress the in vivo response. Moreover, immunization of the donors of suppressor T cells increases the number of splenic CD8-I- suppressor T cells that suppress specifically DTH in the LTS [R.E. Cone, Y. Lemire, and R. Sharafieh, unpubl. observations]. These observations are consistent with those demonstrating that antigen-specific CD8+ suppressor T cells are amplified by immunization [3]. 

The mechanisms of the influence of the SNS on the induction of CD8+ Tregs are likely directed towards both the activation and function of these cells (fig. 2). Sympathetic neurons are a source of (i) norepinephrine that has strong immunoregulatory effects [35] including the proliferation of liver NKT cells necessary for the initiation of contact sensitivity reactions (ii) immunomodulatory NPY [38] that may promote the production of IFN-y necessary for the function of CD8+ suppressor T cells (see below), and (hi) tissue plasminogen activator (t-PA) [41] that converts plasminogen to plasmin that in turn is an activator of immunosuppressive TGF-(3 [42]. 

Qa-1 Restriction ofCD8+ Suppressor T-Cell-Mediated Suppression... 

Antibodies to CD94 and NKG2A receptors for Qa-l and to Qa-l inhibit the in vivo suppression of DTH by AC-SPL cells when the antibodies are included in the inoculum of AC-SPL cells injected into a DTH challenge site [49]. Moreover, splenic CD8+ suppressor T cells can-... 

Fig. 3. Proposed suppressive mechanism of CD8+ suppressor cells. The TCR of suppressor cells engages Qa-1/peptide (TCR V-region ) on a T effector cells or antigen presenting cells. CD94/NKG2A also engages Qa-1. Engagement of the entire complex triggers the secretion of TGF-p by the suppressor T cell that suppresses the effector cell that induces the DTH reaction.

Fig. 4. Cell interactions, cell surface determinants and cytokines in the ACAID pathway to CDS suppressor T cells. 

IFN-y Facilitates the Suppression ofDTFl by Splenic CD8+ Suppressor T Cells IFN-y, a major cytokine in cell-mediated immunity, has been shown to also exert strong down-regulatory effects on cell-mediated autoimmunity... 

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