CD80/CD28 co-stimulation in human brucellosis

Abstract

SummaryDespite treatment, 10-30% of brucellosis patients develop chronic disease, characterized by atypical clinical picture and/or relapses. A defective T helper 1 (Th1) response and a long percentage of CD4 + /CD25 + cells have been described in chronic brucellosis patients. CD80/CD28 co-stimulation is critical for an efficient Th1 response and has not been studied previously in human brucellosis. In order to investigate the role of CD80/CD28 co-stimulation, 13 acute brucellosis patients (AB), 22 chronic brucellosis patients (CB, 12/22 relapsing type-CB1 and 10/22 atypical type-CB2), 11 'cured' subjects and 15 healthy volunteers (controls) were studied. The percentage of CD4 + /CD28 + T lymphocytes and CD14 + /CD80 + monocytes were analysed by flow cytometry both ex vivo and after phytohaemagglutinin (PHA)-stimulation with or without heat-killed Brucella abortus (HkBA). Ex vivo analysis showed no differences between all groups studied. PHA stimulation up-regulated the percentage of CD80 + monocytes in AB compared to 'cured' subjects and controls (P < 0·001), although the proportion of CD4 + / CD28 + cells did not alter. A higher percentage of CD80 + monocytes was observed in the CB1 subgroup, compared to AB, 'cured' subjects and controls (P = 0·042, < 0·001 and < 0·001, respectively). CB2 was characterized by a lower percentage of CD80 + monocytes in comparison to CB1 (P = 0·020). HkBA in PHA cultures down-regulated the percentage of CD80+ monocytes compared to PHA alone in all groups, especially in AB and CB patients (P < 0·001 and P = 0·007, respectively). In conclusion, the diminished percentage of CD4 + /CD25 + T cells in CB is not associated with inadequate CD80/ CD28 co-stimulation. We speculate that differential frequency of CD80 + monocytes after PHA stimulation could serve as a qualitative parameter of disease status, related to the different clinical forms of chronic brucellosis.

Chronic Brucellosis Patients Retain Low Frequency of CD4+ T-Lymphocytes Expressing CD25 and CD28 afterEscherichia coliLPS Stimulation of PHA-Cultured PBMCs

“…In our previous study [23], HKBA stimulation of PHA-cultured PBMCs did not increase the frequency of CD4+/CD28+ T-cells in chronic relapsing brucellosis (Table 3(b)). …”

“…Patients were divided in acute (AB) and chronic (CB) brucellosis groups according to disease history, clinical picture, and laboratory findings [21, 23]. …”

“…When we studied CD80/CD28 costimulation in human brucellosis, it was indicated that heat-killed B. abortus (HKBA) significantly downregulated the PHA-induced increase of CD80+ monocytes [23]. This effect could be attributed to Brucella lipopolysaccharide (LPS) which is thought to be one of the virulence factors that endow the pathogen with the ability to escape the immune [8, 15, 24].…”

DiscordantBrucella melitensisAntigens Yield Cognate CD8+T Cells In Vivo

“…Antibiotic treatment exists but is costly and prolonged, lasting at least 6 weeks in moderate cases, and it may extend for years depending on complications that arise. Even after treatment, PCR data have revealed that low levels of bacteria are detectable years after the resolution of symptoms, and relapses occur in 5 to 30% of cases (20,30,55,62). In areas where brucellosis is endemic, prevention of infection via vaccine would be far more cost-effective than the regimen of antibiotics suggested by the World Health Organization (WHO).…”

Vaccines and Vaccine Candidates against Brucellosis

“…It has been reported that despite early diagnosis and treatment, chronic disease develops in 10-30% of the cases, and approximately 2% of untreated patients die from brucellosis (8,9). In the zoonotic hosts, Brucella spp.…”