Defective IL-6 secretion in HIV-infected haemophilia patients

Abstract

SUMMARY To study the role of IL‐6 in HIV‐induced B cell defects, in vitro B cell responses and IL‐6 secretion were determined simultaneously in 67 haemophilia patients, Twenty‐three palients were HIV (Group 1). 27 HIV+ stage CDC II, III (Group 2). and 17 vi‐ere HIV4 stage CDC IV (Group 3). Pokeweed mitogen (PWM) was used forTeelI‐dependent and Staphylococcus aureus Cowan 1 (SAC I) for T cell‐independent B cell stimulalion. B cell differentiation was assessed in a reverse haemolytic plaque assay and by ELISA determination of IgG and IgM in culture supernatants. An ELISA was used to measure IL‐6 in plasma and culture supernatants, HIV+ patients showed impaired immunoglobulin‐secreting cell (ISC) responses after T cell‐independent and T cell‐dependent stimulation (P < 0·000l and P<0·01, respectively), whereas IL‐6 secretion. IgM and IgG responses were comparable to those in hcallhy controls. HIV+ patients at stage CDC II, Ml or IV demonst rated significantly reduced mitogen‐stimulated IL‐6 secretion (P < 0·05. PWM; P < 0·001. SAC lj as well as impaired ISC and IgG responses (P < 0·01. PWM; P≤ 0·0001, SAC I), CDC IV patients showed reduced IgM responses in addition (P < 0·02, PWM; P < 0·0005. SAC I). Plasma iL‐6 levels were elevated both in HIV* patients (CDC II. Ill patients: 165 ± 73 pg/ml. P < 0·005; CDC IV patients: 58 ± 18 pg/ml, P < 0·001) and in HIV patients (283 ± 65 pg/ ml. P<0·0001) which appeared to be a T cell effect induced by treatment with haemophilia factor concentrates. Our data provide evidence for different types of B cell deficiencies in HIV patients (impaired ISC response only) and HIV+ patients (impaired ISC as well as IL‐6 and IgM /lgG responses). The defective IL‐6 secretion in HIV+ patients is likely to affect terminal B cell differentiation and this may explain the reduced immunoglobulin secretion in these patients in response to antigenic challenge.

HIV-Specific CD8+T Lymphocytes in Blood of Long-Term HIV-Infected Hemophilia Patients

“… 1–3 During 30 years of follow-up, we observed that patients developed autoantibodies against CD4 + T lymphocytes, alloantibodies against HLA, autoantibodies against IgG and Fab, CD4 helper cell defects, cytokine abnormalities, macrophage and CD4 + lymphocyte dysfunctions associated with surface gp120-complement complexes, increased soluble Fas plasma levels, and apoptotic and nonapoptotic CD4 + T-cell depletion; during highly active antiretroviral therapy (HAART), they had decreasing sCD30 plasma levels and increasing dendritic cells (DC) and regulatory T-cell (Treg) blood levels. 1–14 Interestingly, long-term HIV + hemophilia patients and HIV − hemophilia patients showed four and two times as many activated CD3 + CD8 + DR + T lymphocytes in the blood, respectively, compared with healthy controls tested in parallel. 4 In a recently published manuscript, 4 we speculated that HIV − hemophilia patients might have an increased cytotoxic T-cell response because they were stimulated by clotting factor preparations, inactivated virus particles contaminating the clotting factor preparations, and chronic virus infections acquired in the era before virus inactivation of clotting factor preparations was practicable.…”