T helper

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

T helper 1 (Thl) CXCR3, CCR5 Thl cells are a subset of CXCR3+ cells... 

Sallusto F, Lenig D, Mackay CR, Lanzavecchia A. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 1998 187 875-883. 

Allograft rejection is thought to be primarily the result of a T helper 1 (Thl)-type immune response. Thl-like T cells often express CXCR3 and CCR5. T... 

With regard to the specific accumulation of effector T cells in the inflamed RA joints, several papers have documented that T cells in the joints of individuals with RA preferentially express CCR5 (36-38). Furthermore, RA (39) and CIA are thought to be a T helper 1 (Thl)-driven diseases (12,40), and expression of CCR5 is considered to be the hallmark of Thl differentiation, both in... 

DC, dendritic cell NK, natural killer Thl, T helper 1 Th2, T helper 2 Treg, T regulatory. 

Siveke, J.T. and Hamann, A. (1998) T helper 1 and T helper 2 cells respond differentially to chemokines. Journal of Immunology 160, 550-554. 

Roman, M. et al., Immunostimulatory DNA sequences function as T helper-1-promoting... 

Ramer-Quinn, D.S., Baker, R.A., and Sanders, V.M., Activated T helper 1 and T helper 2 cells differentially express the P-2-adrenergic receptor A mechanism for selective modulation of T helper 1 cell cytokine production, J. Immunol., 159, 4857,1997. 

Vandebriel, R.J. et al., Assessment of preferential T-helper 1 or T-helper 2 induction by low molecular weight compounds using the local lymph node assay in conjunction with RT-PCR and ELISA for interferon-y and interleukin-4. Toxicol. Appl. Pharmacol., 162, 77, 2000. 

IRIV Induce a Cytokine Expression Profile Consistent with a T Helper 1 Response... 

The induction of CD4+ T helper 1 responses suggests that IRIV could provide adjuvance to the generation of HLA class I-restricted CTL responses. Thus, we addressed the capacity of IRIV to enhance the induction of CTL specific for influenza matrix (IM) 58-66 epitope and Melan-A/Mart-127-35 melanoma-associated epitope. Briefly, CD 14-cells isolated from healthy donor s peripheral blood were cocultured with autologous iDC in presence of peptide and empty IRIV or in presence of peptide alone. 

The T-helper cells are further divided into two types, T-helper 1 (ThI) and T-helper 2 (Th2) (see below for discussion). Of the total lymphocyte population in the body (approx. 10 cells), the proportion of T-cells is 50-60%, that of B-cells is 10-15% and that of natural killer cells is <10%. 

Cohn L, Homer RJ, Niu N, Bottomly K. 1999. T helper 1 cells and interferon regulate allergic airway inflammation and mucus production. J Exp Med. 190 1309-1317. 

Herbert, D.R., Holscher, C., Mohrs, M., Arendse, B., Schwegmann, A., Radwanska, M., Leeto, M., Kirsch, R., Hall, P., Mossmann, H., Claussen, B., Forster, I. and Bronbacher, F. (2004) Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity 20, 623-635. 

Figure 22.2 Cellular activation by CpG DNA. CpG DNA directly activates dendritic cells (DCs), monocytes and macrophages, to express increased levels of co-stimu-latory molecules, to increase antigen presentation, and to secrete high levels of chemokines and cytokines, such as interleukin 12 (IL-12), interferon-a(IFN-a), and tumor necrosis factor-a (TNF-a), and monocytes and macro-phages have increased antibody-dependent cellular cytotoxicity (ADCC) activity. NK cells are induced to express IFN-7 by these cytokines acting in concert with CpG, and have increased lytic activity. B cells rapidly produce IL-b and IL-10 and express increased levels of costimulatory molecules. B cells rapidly enter the cell cycle and become resistant to some forms of activation-induced cell death. T cells are not directly activated by CpG, but because of the T helper 1 (Thl)-like cytokine environment, and the increased antigen presenting cell (APC) activity, antigen-specific Thl cells and cytotoxic T lymphocytes (CTL) are generated.

Roman, M., Martin-Orozco, E., Goodman, J.S., Nguyen, M.D., Sato, Y., Ronaghy, A. etal. (1997) Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nat. Med., 3, 849-854. 

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