Association of immune complexes and plasma viral load with CD4 + cell depletion, CD8 +DR + and CD16 + cell counts in HIV + hemophilia patients. Implications for the immunopathogenesis of HIV-induced CD4 + lymphocyte depletion

Abstract

Objective: There is evidence that HIV induces CD4 + depletion in part by the formation of immune complexes (IC) that attach to CD4 + blood lymphocytes. In the present study we examined the relationship of IC-coated CD4 + blood cells with retroviral replication in HAART-treated patients. Patients and methods: 52 hemophilia patients were studied from 1997 to 1999. Lymphocyte subsets, IgM, IgG and gp120 on CD4 + blood cells, in vitro responses of lymphocytes to mitogens, plasma neopterin and plasma viral load were measured. Results: Patients with detectable viral replication and without ICs on CD4 + blood lymphocytes had a lower viral load (4100 versus 21000 HIV-1 mRNA copies/ml; P=0.079) and higher CD4 + cell counts (310/μl versus 161/μl; P=0.035) than patients with ICs on circulating CD4 + lymphocytes. Among patients with <80 HIV-1 mRNA copies/ml, IC − individuals had slightly higher CD4 + lymphocyte counts than IC + patients (384/μl versus 316/μl; n.s.). Further evidence for the clinical relevance of the ICs was obtained when 18 patients who had an undetectable viral load at previous investigations were analyzed. Among patients with a stable undetectable viral load, CD4 + counts increased in 6 of 8 IC − but in none of 2 IC + individuals. In patients whose viral load increased during the observation period, 5 of 6 IC − but none of 2 IC + individuals showed higher CD4 + cell counts. Impaired virus killing is suggested by lower CD16 + (35/μl versus 107/μl; P=0.016), higher CD3 +DR + (178/μl versus 66/μl; P=0.006), and higher CD8 +DR + (142/μl versus 34/μl; P=0.017) cell counts in IC − patients compared to IC − patients without detectable viral load. Strong retroviral replication induced strong T cell dysfunctions. Fewer CD3 +25 + blood lymphocytes (19/μl versus 47/μl; P=0.006) and a lower in vitro response of T lymphocytes to the mitogens Con A (RR: 0.3 versus 1.2; P=0.023) and CD3 mab (RR: 0.5 versus 2.4; P=0.012) was observed in IC + patients with detectable versus undetectable viral load. Conclusion: Our data suggest that ICs on circulating CD4 + blood lymphocytes are primarily associated with CD4 + lymphocyte depletion whereas the plasma viral load is primarily associated with decreased T lymphocyte activation, lower CD16 + counts, and higher CD8 +DR + lymphocytes which might be the effector cells for virus elimination.