Regulatory CD8 T Cells

Treg cells in mice are divided into at least two groups Qa-1 restricted and Qa-1 nonrestricted Qa-1 is an equivalent of human HLA-E. 

The generation and function of CD8+ Treg cells is less defined than that of CD4+ Treg cells. It is well established that Treg cells induce tolerance by controlling autoreactive T cells that were not deleted in the thymus. Although CD4+CD25+ 

Treg cells are generated in the thymus, the site of origin of CD8+ Treg cells has not been determined. 

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Tang XL, Smith R, Kumar V Specific control of immunity by regulatory CD8 T cells. CeU Mol Immunol 2006 2 1-9. 

Diaz-Sanchez, D., Noble, A., Staynov, D.Z., Lee, T.H. and Kemeny, D.M. (1993b). Elimination ofIgE regulatory CD8 T cells in vivo difierentially modulates the ability of spleno-cytes to produce IL-4 and IFN7 but not 11 2. Immunology 78, 513-519. 

Field AC, Caccavelli L, Bloch MF, Bellon B (2003) Regulatory CD8+ T cells control neonatal tolerance to a Th2-mediated autoimmunity. J Immunol, 170(5) 2508-2515. 

In vitro TGN1412 caused a profound, polyclonal T-cell proliferation of human peripheral blood mononuclear cells, including those from patients with BCLL. It also induced a profound activation and proliferation of T-cell subsets including CD4+ and CD8+ T cells, naive and memory T cells, and regulatory T cells. TGN1412 was shown to induce a transient, well tolerated expansion of T cells in nonhuman primates treated with TGN1412 and efficacy was demonstrated in a rhesus monkey collagen-induced arthritis model. 

Dubois B, Chapat L, Goubier A, Papiernik M, Nicolas J-F, Kaiserlian D Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation. Blood 2003 102 3295-3301. 

Franzece O, Kennedy PTF, Gehring AJ, Gotto GM., et al. 2005. Modulation of the CD8+ T cell response by CD4+CD25+ regulatory T cells in patients with Hepatitis B virus infection. J Virol. 79 3322-3328. 

Grdic D, Homquist E, Kjerrulf M, Lycke NY Lack of local suppression in orally tolerant CD8-deficient mice reveals a critical regulatory role of CD8+ T cells in the normal gut mucosa.. 1 Immunol 1998 160 754-762. 

As mentioned above, CD8+ T cells induced in SAg responses may kill activated CD4+ T cells and therefore perform a regulatory function in the response. Further, Swain and coworkers [35] have reported that CD4-CD8-cells suppressed CD4+ T cells in an IFN-y-dependent way. A subsequent study from the same laboratory provided evidence that myeloid cells mediated that regulatory mechanism [115],... 

XU, H DILULIO, N.A. FAIRCHILD, R.L. (1996) T cell populations primed by hapten sensitization in contact sensitivity are distinguished by polarized patterns of cytokine production. Interferon-y-producing (Tel) effector CD8+ T cells and interleukin (IL) 4/IL-10-producing (Th2) negative regulatory CD4+ T cells. Journal of Experimental Medicine, 183,1001-1012. 

The ability to induce immune tolerance to D-pen by pretreating BN rats with low dose D-pen prior to high dose D-pen has yielded additional evidence that cytokines might play a role in determining susceptibility to DIAI (Masson and Uetrecht 2004). Specifically, low dose tolerance to D-pen is associated with increased expression of the regulatory cytokines, IL-10 and TGF-p, in splenic CD4 and CD8 T cells (Donker et al. 1984 Masson and Uetrecht 2004). Both of these cytokines have been shown to suppress disease in other models of autoimmunity (Blenman et al. 2006 Rubtsov and Rudensky 2007). Thl cytokines also appear to be involved in the mechanism of immune tolerance to D-pen, as low dose pretreatment increased IFN-y expression in CD8 T cells (Masson and Uetrecht 2004). These observations indicate that regulatory and Thl cytokines might be at least partially responsible for the resistance to D-pen-induced autoimmunity. 

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