Activation–mediated CD4+ T cell unresponsiveness during acute Toxoplasma gondii infection in mice

Abstract

Infection of mice with Toxoplasma gondii has been shown to induce a transient state of immune down-regulation. Earlier reports have demonstrated the role of cytokines, in particular IL-10, in this host response. Here evidence is presented that T.gondll, a major opportunistic pathogen of the newborn and those with AIDS, is able to induce CD4⁺ T cell population Increased in volume by day 7 post-infection and expressed T cell maturation markers (CD44^hl, Il-2r^hl,Mel-14^fo). Further noted was a clonal activation of several CD4+ T cells subsets expressing the V_β chain of the TCR. At day 7 post-infection, partial reduction of all CD4⁺ T cells to mltogen or parasite antigen stimulation was observed, In particular V_β5 T cells. Addition of rlL-2 partially restored the CD4⁺ T cell proliferative response in Vitro. The T cell activation marker CTLA-4 could not be detected and te co-stimulatory molecule, CD28, was down-regulated. Elctrophonetic and morphologic analysis of these cells post0culture demostrated a DNA fragmentation pattern and cell death consistent with apoptosis. These studies demonstrate for the first time in a protozoan parasite that activation-induced CD4⁺ T cell unresponslveness occurs during actue T.gondll infection in mice, and may be important in immune down-regulation and parasite persistence in the infected host.0