JOHN LOUIS STERNICK, Marquette University


Although granulomatous inflammation is found in many human diseases, its pathological mechanism is ill-defined and many of these diseases do not have a known cause. More recently, the role played by lymphokines, macrophages and lymphocytes in granulomatous inflammation has come under immunological investigation. Also, few studies have been performed on the possible role of hereditary factors in this disease process. Using a known inflammatory agent, such as BCG, which classically causes granuloma formation, the role of T-lymphocytes and hereditary factors in this inflammatory process can be studied. Inbred mouse strains vary in the development of granulomatous inflammation induced by the intravenous injection of BCG in an oil-in-saline mixture. C57 BL/6 and CBA mice are known to be high and low responder, respectively, because the high responder develops intense granulomatous inflammation of the lung and splenomegaly while the low responder does not. There are mice, such as the BALB/c, which develop an intermediate granulomatous inflammation under the same experimental conditions. BCG-induced granulomatous inflammation of the lung and splenomegaly in the C57BL/6 mouse is T-cell dependent since "B" mice (mice with reduced number of T-cells) do not develop an intense inflammatory response. When "B" mice were reconstituted with thymocytes, whole spleen cells or nylon wool purified spleen cells (the first and latter cell types are mostly T-cells) and injected with BCG, they totally regain the ability to form granulomatous inflammation in the lung but only partially regain the capacity to display splenomegaly. Breeding studies between C57BL/6 and CBA mice encompassing F(,1), F(,2) and backcrosses showed that the response to BCG in the lung and spleen is polygenic, incompletely dominant, and seemingly under the control of recessive and dominant regulatory genes. The use of recombinant inbred (RI) BXD mice indicated that granulomatous inflammation in the lung and splenomegaly is linked to the immunoglobulin heavy chain (Igh) complex of the C57BL/6 mouse. This was confirmed for the spleen with the use of the following congenic mice: BALB/c.Ig('b), CB-20, and BAB-14. Similar studies with congenic mice suggested that genes within the Igh complex do not influence the development of granulomatous pulmonary inflammation. There was no association between the response of BCG either in the lung or spleen and theH-2 complex using BXD RI mice suggesting that genes with the major histocompatibility complex do not influence responsiveness to BCG. These studies indicate that granulomatous inflammation of the lung and splenomegaly is mediated by T-lymphocytes and controlled by hereditary factors, two of which are associated with the Igh complex. However, the mechanism of cellular interaction and the finding of other genetic loci involved in this type of inflammation is important in order to fully understand this pathological condition. Eventually, additional studies in this animal model may provide a more complete understanding of the immunology and genetics of chronic granulomatous inflammation. This information, in turn, should be applicable to studies of granulomatous inflammation in man.

Recommended Citation

JOHN LOUIS STERNICK, "IMMUNOGENETICS OF BCG-INDUCED GRANULOMATOUS INFLAMMATION OF THE LUNG AND SPLENOMEGALY" (January 1, 1980). Dissertations (1962 - 2010) Access via Proquest Digital Dissertations. Paper AAI8111869.