Immunoregulation of granuloma formation in murine schistosomiasis mansoni

Abstract

Schistosomiasis mansoni is a chronic, T lymphocyte-mediated granulomatous disease that affects mainly the liver and intestines of the infected host. The chronic inflammatory process and subsequent fibrous repair are the major factors in the pathology of the disease. In the murine model of schistosomiasis at the onset of the chronic stage of the infection, the granulomatous response undergoes spontaneous modulation with concomitant alleviation of the pathologic disturbance. Analysis of the process of modulation revealed that it results from the interaction between inflammatory and regulatory subpopulations of T lymphocytes. At the acute phase of the infection, the granulomatous response is initiated and maintained by inflammatory TDH cells that release lymphokines which mobilize and recruit the macrophages, eosinophils, etc. for the generation of the lesion. Already at this stage, while the inflammatory influence prevails, a low number of suppressor T lymphocytes are present. With the progress of the infection, the overheated inflammatory response is curbed by regulatory processes. At least two, but perhaps more, T suppressor lymphocytes are involved in the maintenance of the modulation of the granulomatous response. Modulation is an active process that needs constant maintenance, probably by recruitment of fresh suppressor cells. Removal of the suppressor population causes an immediate elevation of the granulomatous response. During modulation, T suppressor lymphocytes either abrogate or greatly diminish inflammatory lymphokine production. This in turn may be the cause for decreased cell recruitment and diminution in newly formed granuloma size. Apparently a total abrogation of the granulomatous response is not desirable because released egg antigens can be harmful to liver parenchyma cells. This has been demonstrated both in thymus-deprived and in nude, infected mice. Thus, a smaller inflammatory response has the double advantage of not only being less destructive, but also shielding the underlying tissue from damage by parasite products. The various subpopulations of T lymphocytes communicate with one another by means of soluble suppressor factors that arise from the suppressor T cells. The factors may have different functions. One factor may regulate lymphokine production whereas another may recruit fresh suppressor cells from a pool of precursors. The factors act in an antigen-specific manner. Tentatively, one may assume that these factors are composed of two units: one is the I subregion membrane marker and the other is the specific recognition receptor. The nature of this receptor is still unclear, but it may be an anti-idiotypic determinant.(ABSTRACT TRUNCATED AT 400 WORDS)