CD80/CD28 co‐stimulation in human brucellosis

Summary Despite 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.