CD4+and CD8+T-cells

Yang YF, Tomura M, Iwasaki M, et al. IL-12 as well as IL-2 upregulates CCR5 expression on T cell receptor-triggered human CD4+ and CD8+ T cells. J Clin Immunol 2001 21 116-125. 

Bradfield PF, Amft N, Vemon-Wilson E, et al. Rheumatoid fibroblast-like synoviocytes overexpress the chemokine stromal cell-derived factor 1 (CXCL12), which supports distinct patterns and rates of CD4+ and CD8+ T cell migration within synovial tissue. Arthritis Rheum 2003 48(9) 2472-2482. 

Koyama, K., Tamanchi, H. and Ito, Y. (1995) The role of CD4+ and CD8+ T cells in protective immunity to the murine parasite Trichuris muris. Parasite Immunology 17, 161-165. 

Dearman, RJ. et al., Allergen-induced cytokine phenotypes in mice role of CD4+ and CD8+ T cell populations, Clin. Exp. Allergy, 35(4), 498, 2005. 

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. 

TCDD (reviewed in13). However, despite considerable effort, direct effects of TCDD on purified T cells in vitro have not been consistently demonstrated, and direct effects on T cells in vivo are difficult to prove. This issue was recently resolved by studies that compared the effects of TCDD on the graft versus host (GVH) response of T cells obtained from AhR+,+ and AhR C57B1/6 (B6) mice.66 Results showed that the CTL response of grafted AhR- - T cells was resistant to TCDD-induced suppression, while under the same conditions, the CTL response of AhR+,+ T cells was suppressed by > 90%. Furthermore, when CD4+ and CD8+ T cell subsets were isolated from AhR+,+ and AhR- - mice and then recombined prior to grafting, full suppression of the CTL was dependent on AhR expression in both T cell subsets. These results provide the first evidence for the requisite role of the AhR in T cells for TCDD-mediated suppression of T cell responses. Induction of CYP1A1 in purified T cells exposed to TCDD in vitro validates the presence of a functional AhR.6-7... 

Kerkvliet, N. I., Shepherd, D. M., and Baecher-Steppan, L., T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD, Toxicol. Appl. Pharmacol., 185, 146, 2002. 

The bronchial lavage of atopic subjects exhibits increased TH2 cytokine (IL-4, IL-5, IL-13) mRNA levels in both CD4+ and CD8+ T cells. 

A recent study has utilized an in vivo murine tumor model expressing human HER-2 for evaluating potential HER-2 vaccines consisting of either full-length or variable subunits of HER-2 delivered in either protein or plasmid DNA form (discussed later) (Foy et al., 2001). The mechanism of protection elicited by plasmid DNA vaccination appears to be exclusively CD4-dependent and not CD8- or antibody-dependent, whereas the protection observed with intracellular domain protein vaccination requires both CD4 and CD8 T cells. However, the exact mechanism(s) responsible for immunity to DNA has not been elucidated. 

Another recent study supports the use of the dendritic cell-based vaccine as a therapeutic strategy to target both CD4 and CD8 T cells to HER-2 (Chen et al., 2001). To minimize the possibility of deleterious effects, the transforming activity of the HER-2 molecule can be inactivated by a single amino acid substitution (lysine to alanine), unlike other studies in which the entire intracellular domain was removed. 

Blanas E, Davey GM, Carbone FR, Heath WR A bone marrow-derived APC in the gut-associated lymphoid tissue captures oral antigens and presents them to both CD4+ and CD8+ T cells. J Immunol 2000 164 2890-2896. 

It is clear that in the NOD mouse model, both CD4+ and CD8+ T cells are involved in ft cell destruction. Athymic NOD mice and NOD.scid mice that lack these cells do not develop insulitis or diabetes, and treatment of NOD mice with anti-CD3 antibodies inhibits the development of disease (Miller et al., 1988 Dardenne et al., 1989 Christianson et al., 1993). Adoptive transfer studies demonstrated that splenic T cells from NOD mice transplanted into young or irradiated NOD mice, transfer diabetes and that the process requires both CD4+ and CD8+ T cells (Thivolet et al., 1991 Yagi et al., 1992 Katz et al., 1993). However, the specific role(s) for these cells in diabetogenesis remain(s) unclear. CD4+ T cells are required for both the activation of CD8+ T cells and for their recruitment into the pancreatic islets (Nagata et al., 1994 Verdaguer et al., 1996). CD8+ T cells clearly play an important... 

Christianson, S. W., Shultz, L. D. and Leiter, E. H. (1993). Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD. NON-Thy-la donors.Diabetes 42, 44—55. 

Ulmer JB, Fu TM, Deck RR, Friedman A, Guan L, DeWitt C, Liu X, Wang S, Liu MA, Donnelly JJ, Caulfield MJ (1998), Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA, J. Virol. 72 5648-5653. 

CD4 and CD8 T cells have different functions when activated. Cytotoxic T lymphocytes (CD8) lyse cells expressing specific viral or tumor antigens. CD8 cells have also been shown to downregulate (suppress) other immune responses under some circumstances, probably by the production of certain cytokines. Hence, they are sometimes referred to as suppressor T cells. CD4 helper T cells consist of two major subpopulations (Figure 32.2). These subpopulations appear to regulate different sets... 

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