The capacity of lymphocytes from blood or lymphoid tissues to respond to chemoattractants is considerably enhanced by a period of 12-48 h of culture in the presence of activating agents. Polyclonal activators such as CD3-specific antibody, phytohemag-glutinin (PHA), concanavalin A (con A), or even fetal calf serum will increase the proportion of locomotor cells from 10% to 30-70%. Antigens such as purified protein derivative of Mycobacterium tuberculosis (PPD) or superantigens such as staphylococcal enterotoxin B (SEB) have a similar effect. These are not direct chemoattractant effects. If the cultured cells are washed and resuspended in the presence of a fresh preparation of the activator, they may show no response, but if they are resuspended in their own supernatant medium, they do respond, suggesting that chemotactic cytokines are released during culture. Both lymphocyte activation and the release of attractants into the supernatant are dependent on the presence of accessory cells and highly purified T cells fail to become activated.
Following culture in the presence of accessory cells, the activated T lymphocytes can be purified and will then show chemotactic responses to pure cytokines (see tables 1 and 2 of the 'Chemotaxis' article). Interleukin 2 (IL-2) and IL-15 are both good chemotactic factors for these cells. The shared j3 chain (and probably also the 7c chain) of the IL-2 and the IL-15 receptor are essential for this activity. The chemotactic activity of IL-15 probably plays a major role in recruitment of T cells into the lesions of rheumatoid arthritis. IL-16 also is a T cell attractant with a selective activity for CD4+ ceils. Several chemokines also have activity. They include the a (C-X-C) chemokines, IL-8, and IP-10 (induced by IFNy), and the j8 (C-C) chemokines, MlP-la and j3, MCP-1, -2, -3 and -4, and RANTES. During activation with PPD, SEB or anti-CD3, as detailed above, sufficiently large quantities of IL-8 are released by monocytes to stimulate locomotion of T lymphocytes. (3 Chemokines have very little activity for T lymphocytes cultured for 24-48 h with the above-mentioned activators, but, during a week of culture with IL-2, the lymphocytes acquire chemokine receptors and show stronger locomotor responses to MIP-1 a and RANTES. The list of presently known attractant cytokines is certainly incomplete. The profusion of lymphocyte attractant factors suggests that each may have specific roles in different types of lesion, but this is conjecture at present.
Was this article helpful?