Demonstration of a T cell growth factor and its relationship to immunoregulation in jirds experimentally infected with Brugia pahangi
Description
The persistence of filarial worms in a host appears to be the result of a balance between host immune responses and direct activation of immunoregulatory mechanisms by parasite antigens. Experimental studies have contributed to the understanding of the immunoregulatory mechanisms apparently activated by filarial antigens. The purpose of the present studies was to further characterize both parasite and host mediated T cell mediated immunoregulatory mechanisms at the level of lymphokine production and lymphokine-cell interactions in Brugia pahangi infected jirds. The results of the present study demonstrate that B. pahangi derived crude soluble extracts suppress the ability of mitogen stimulated normal jird lymphocytes to produce a T cell growth factor with IL-2-like activity (IL-2). In addition, microfilarial fractions higher than 150 Kd, purified by gel filtration HPLC, consistently suppressed antigen as well as mitogen reactivity. However, the in vivo relevance of these findings requires further investigation. The regulation of lymphokine production in B. pahangi infections was examined in in vitro IL-2 and lymphocyte transformation assays. Spleen cells from microfilaremic jirds, in contrast to spleen cells from jirds with prepatent infection, did not produce significant levels of IL-2 in response to parasite antigen. Evidence that this deficiency was an active cell mediated regulatory event was obtained in cell depletion and add-mixture experiments. In IL-2 binding assays, $\sp{125}$I-IL-2 specifically bound IL-2 receptors (53-67 Kd) on activated jird lymphocytes. Although the proliferative responsiveness of spleen cells from microfilaremic jirds to B. pahangi antigen was suppressed, the levels of high affinity IL-2 receptor expression on these cells were comparable to those of antigen stimulated lymph node cells from the same animals. The results of the present study support the hypothesis that parasite activated immune modulatory mechanisms are cell mediated, are associated with the presence of microfilariae in blood, and with an inability of lymphocytes to produce IL- 2, but not to express IL-2 receptors