Association of granulysin, perforin, ifn-γ and lymphocyte subsets influences the clinical outcome in thai patients with tb and hiv/tb coinfection

Abstract

Host effector mechanism against Mycobacterium tuberculosis infection is dependent on innate immune response by macrophages and neutrophils and alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their potential role in clinical tuberculosis is still controversy. This study aims to investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9+Vδ2+ T cells, CD4+ T cells and CD8+ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection who have been living in Chiang Rai, north of Thailand where TB is endemic. Granulysin and perforin levels in TB patients were lower than healthy controls, whereas much higher granulysin levels in HIV/TB coinfection than in any other groups, TB and HIV with or without receiving HAART were noted. Such higher levels corresponded to the number of CD8+ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed. The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection.