Alterations in lymphocyte phenotype and function in children with shigellosis who develop complications

Abstract

This study was designed to see whether alterations occur in peripheral blood mononuclear cell phenotype and function in children with Shigella dysenteriae 1 infection with complications (leukemoid reaction and/or hemolytic-uremic syndrome) and whether there are any alterations prior to the development of complications. The following groups of children (ages, 12 to 60 months) were compared: children without any infection (n ‫؍‬ 51), children with uncomplicated shigellosis (n ‫؍‬ 65), children admitted with complicated shigellosis (leukemoid reaction and/or hemolytic-uremic syndrome) (n ‫؍‬ 29), and children with shigellosis who developed complications after enrollment (subsequently complicated shigellosis) (n ‫؍‬ 12). Tests for the peripheral blood mononuclear cell phenotype (CD3, CD4, CD8, CD16, CD20, and CD25), spontaneous proliferation, and the proliferative response to phytohemagglutinin, pokeweed mitogen, and the lipopolysaccharide of S. dysenteriae 1 were performed, as were skin tests for delayed-type hypersensitivity (DTH). Children who subsequently developed complications differed from other groups of children as follows: (i) the numbers of CD3 ؉ and CD4 ؉ cells were lower than in uninfected children (P < 0.05), (ii) the CD4/CD8 ratio was lower than in children with uncomplicated shigellosis (P < 0.05) and in uninfected children (P < 0.05), and (iii) the levels of spontaneous proliferation of peripheral blood mononuclear cells were higher and DTH responses were lower than those in children with uncomplicated shigellosis (P < 0.05 and P < 0.017, respectively). Children with complications differed by having (i) increased numbers of CD3 ؊ CD16 ؊ CD20 ؊ cells (P < 0.05) compared with those in other groups of children and (ii) lower CD4/CD8 ratios (P < 0.05), higher levels of spontaneous proliferation (P < 0.05), and lower DTH responses (P ‫؍‬ 0.005) than children with uncomplicated shigellosis. Three to five days after enrollment, the number of CD4 ؉ cells increased in children who subsequently developed complications (P ‫؍‬ 0.025), i.e., when they developed complications and at this time their CD4 ؉ cell number was similar to that of other groups of children. Thus, lymphocyte phenotype and function are altered prior to the development of complications in children with shigellosis, and once complications develop, the pattern of alterations changes. Whether these alterations have a role in precipitating complications or whether they reflect early events underlying the development of complications remains to be elucidated.

Immune Response of Children Who Develop Persistent Diarrhea following Rotavirus Infection

“…Assays to determine general immune response. The proliferative response of PBMs was assessed on resting cells by measuring spontaneous DNA synthesis as described previously (3). Results were expressed as counts per minute.…”

Host Receptor Immunomodulation in Response to <i>Shigella</i> Surface Antigens: An Insight for Vaccine Development

“…Immunity to Shigella infection is mainly characterized by sensitized T-cells (Islam et al, 1995a;Raqib et al, 1994) since there is increased inhibition of DTH (Mukhopadhaya et al, 2003;Mulczyk et al, 1987) and inflammatory cytokines (Raqib et al, 1995a;1995b;1995c;Way et al, 1998). Since protective immunity to shigellosis is delayed, patients may thus develop severe clinical complications (Azim et al, 1996;Raqib et al, 2002). Subcellular basis of Shigella destruction as well as immunological basis of T-cell suppression either in acute or chronic Shigella infection is not yet completely understood.…”

“…Subcellular basis of Shigella destruction as well as immunological basis of T-cell suppression either in acute or chronic Shigella infection is not yet completely understood. However, studies on T-cell subsets suggest a biased induction of Th2 (Azim et al, 1996;Islam et al, 1995b). Therefore, lack of protective Th1 response during most of the experimental studies suggests a nature of T-cell suppression (Barman et al, 2011).…”

“…While their role in host defense mechanism are not well defined, it is known that the primary cytokines like MIF and MAF are released from the macrophages and are essential for the activation of class-II antigens with T-cell (Bagchi and Sinha, 2004). During T-cell activation, pro-and anti-inflammatory cytokines such as IL-2, IL-4, IFN-γ and IL-10 are released (Azim et al, 1996;Bagchi and Sinha, 2004;Islam et al, 1995a;Raqib et al, 1994) -this might help in CyRs activation resulting in memory T-cell activation and differentiation. Earlier, the concentration of IL-2 induced by a major OMP was determined in natural infection (Chakrabarti and Sinha, 1997).…”

Role of anti-CD3 in modulation of Th1-type immune response in Shigella dysenteriae infection

“…In shigellosis, immunity to Shigella infection is mediated mainly by sensitized T-cells (Acha-Orbea, 1993;Herman et al, 1991). This has been well documented by inhibition of delayed type hypersensitivity, immuno-proliferative responses and in cytokine functions (Sinha et al, 1994;Azim et al, 1996;Raqib et al, 1995). The protective immunity often appears late, as a result of which patients may develop some clinical manifestations (Bhattacharya et al, 1988).…”