Tcell subsets

Andiieu )M, Even P, Venec A, Tourani JM, Stem M, Lowenstein W, Audroin C, Erne D, Masson D, Sots H, Israel-Biet D, Beldjord K. Effects of cyclosporin on Tcell subsets in human immunodefciency virus disease. Clitt Immunol Immunopaihol 1988 47 181-198. Katpas A, Lowdell M, Jacobson SK, Hill F. Inhibition of human immunodeficiency vitus and growth of infected T cells by the immunosuppressive drugs cyclosporin A and FK 506. Proc Natl Acad Sci USA 1992 89 8351-8355. 

The various organs of the immune system such as spleen, lymph nodes, thymus and bone marrow containing the cells involved in the various immune responses offer the possibility to harvest these cells and perform in vitro assays for evaluation of effects on the immune system. When part of an in vivo animal study this may indicate a direct toxic effect of pharmaceuticals, that is, immunosuppression (Table 18.2). So, it is feasible to obtain cell suspensions for further evaluation such as determination of cellular subsets of T and B leukocytes by fluorescent activated cell sorter analysis (FACS analysis), and determination of natural killer (NK) cell activity of the spleen cell population. An advantage of this approach is that it may lead to identification of a biomarker to be used in clinical studies. In addition, in vitro stimulation of spleen cells with mitogens activating specific subsets may indicate potential effects on the functionality of splenic cell populations. Concanavalin A (Con A) and phytohemagglutinin (PHA) activate Tcells, while lipopolysaccharide (LPS) activates primarily B cell populations. Blood is collected for total white blood cell (WBC) determination and blood cell differential count. In addition, serum can be obtained for determination of serum immunoglobulins. 

Memory CD4 and CD8 T cells can be divided in effector and central memory Tcells. Effector memory cells are thought to home to nonlymphoid tissues, whereas the central memory T cells localize more to secondary lymphoid tissue [29]. Although originally distinguished by the expression of CCR7 by the central memory T cells, it is clear that both subsets express CCR7 [29, 34]. However, it is thought that these memory cells can express every appropriate chemokine receptor [29]. 

In general, CXC chemokines are attractants for neutrophils and T lymphocytes and ELR-CXC chemokines are attractants for B and T lymphocytes (Table 6.1). CC chemokines induce chemotaxis of multiple subsets of white blood cells, such as monocytes, basophils, dendritic cells, macrophages, NK cells and Tcells (Table 6.2). C chemokines are important for T cells traveling to the thymus and the CX3C chemokine, fractalkine, also acting as an adhesion molecule, seems to be important for the infiltration of T cells, NK cells and monocytes (Table 6.3). 

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