T helper cell responses

Stimulation for 24 hours with LPS leads to the release of interleukin-1 [3, IL-6, IL-8, TNF-a and by prolonging the incubation period from 48 to 72 hours, the whole blood model can detect the release of other lymphokines [45], including IL-2, IL-4, IL-13 and IFN-y. Skewing of the T-helper cell response to antigens can likewise be detected by evaluating the pattern of cytokine release, corresponding to a predominance of Th 1 or Th2 cytokine production. The predictive value of these approaches is currently under investigation. 

Regnstrom, K., Ragnarsson, E.G.E., Koping-Hoggard, M., Torstensson, L., Nyblom, N., and Artursson, P. (2003) PEI—a potent, but not harmless, mucosal immunostimulator of mixed T-helper cell response and EasL mediated cell death in mice. Gene Ther. 10,1575-1583. 

TCDD levels in the blood or the age of the person and the respective proliferative capacity of their lymphocytes. However, exposed subjects showed a reduced response to human lymphocyte antigen-allogeneic lymphocytes and interleukin-2-boosted proliferation. According to Tonn et al. (1996), this suppression is indicative of a reduced T-helper cell response, although the actual number of T-helper cells was not altered by 2,3,7,8-TCDD. The authors concluded that 2,3,7,8-TCDD immunosuppression is more likely mediated by a reduced functionality of individual cells rather than by a reduction in numbers of cells circulating in the blood. Tonn et al. (1996) further noted that the changes in immunocompetence observed did not correlate with obvious diseases related to severe immunodeficiency such as certain cancers and infections. 

At present, the aim is to ensure that a humoral response is generated. For mucosal vaccines, IgA may be more appropriate.21516 T cell-mediated responses may also be considered, and advances in knowledge and the development of different types of vaccines and/or adjuvants suggest that cell-mediated responses may be just as or more important than the humoral response, when considering the selection of species. Adjuvants can selectively switch the T helper cell response, which may influence a protection or pathology dependent response (see Section 19.2.5). However, the current understanding and interpretation of such data are limited in terms of predicitivity, and there are also limitations in the immunoassays developed for species routinely used in nonclinical testing. This is a key area where further development is required. 

Bright, H., Turnbull, T., Toms, G. L., and Scott, R. (1995). Comparison of the T helper cell response induced by respiratory syncytial virus and its fusion protein in BALB/c mice. Vaccine 13, 915. 

Cairns LS, Phelps RG, Bowie L, et al. The fine specificity and cytokine profile of T-helper cells responsive to the o3 chain of Type IV collagen in Goodpasture s disease. J Am Soc Nephrol 2003 14 2801-2812. 

Bonecchi R, Bianchi G, Bordignon PP, et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (This) and Th2s. J Exp Med 1998 187 129-134. 

T Helper Cell Cytokine Responses During Intestinal Nematode Infection Induction, Regulation and Effector Function... 

Artis, D., Humphreys, N.H., Bancroft, A.J., Rothwell, N.J., Potten, C.S. and Grencis, R.K. (1999a) TNF-a is a critical component of IL-13-mediated protective T helper cell type 2 responses during helminth infection. Journal of Experimental Medicine 190, 953-962. 

Harris, N.L., Peach, R.J. and Ronchese, F. (1999) CTLA-4-Ig inhibits optimal T helper cell development but not protective immunity or memory response to Nippostrongylus brasiliensis. European Journal of Immunology 29, 311-316. 

Tsuyuki, S., Tsuyuki, J., Einsle, K., Kopf, M. and Coyle, A.J. (1997) Co-stimulation through B7-2 (CD86) is required for the induction of a lung mucosal T helper cell 2 (Th2) immune response and altered airway responsiveness. Journal of Experimental Medicine 185, 1671-1679. 

Aoki, I., Itoh, S., Yokota, S., Tanaka, S.I., Ishii, N., Okuda, K., Minami, M. and Klinman, D.M. (1999) Contribution of mast cells to the T helper 2 response induced by simultaneous subcutaneous and oral immunization. Immunology 98, 519-524. 

IL-2, also known as T-cell growth factor, represents the most studied member of the interleukin family. It was the first T-cell growth factor to be identified and it plays a central role in the immune response. It is produced exclusively by T-lymphocytes (especially T-helper cells), in response to activation by antigen and mitogens. 

It is also more or less accepted that T-cells, in particular T-helper cells (CD4+), may develop into either Thl cells or Th2 cells. By doing so, T-helper cells orchestrate the ensuing immune response by the types of cytokines they produce. Thl cells, by producing IL-12 and y-IFN, stimulate macrophages and/or cytotoxic T-cells to kill and destroy infected or malignant cells, or to initiate a delayed type hypersensitivity (DTH) reaction Th2 cells, by producing IL-4, IL-5, IL-10, IL-13, trigger B-cells to initiate antibody production. 

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