Details

Autor(en) / Beteiligte

• DANIEL, V.
• SADEGHI, M.
• NAUJOKAT, C.
• WEIMER, R.
• HUTH‐KÜHNE, A.
• ZIMMERMANN, R.
• OPELZ, G.

Titel

Evidence for autoantibody‐induced CD4 depletion mediated by apoptotic and non‐apoptotic mechanisms in HIV‐positive long‐term surviving haemophilia patients

Ist Teil von

• Clinical and experimental immunology, 2004-01, Vol.135 (1), p.94-104

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• SUMMARY It is believed that autoimmune phenomena and apoptosis contribute to CD4 depletion. We investigated 11 long‐term (>20 years) HIV‐infected haemophilia patients and 10 healthy controls. Using four‐colour‐fluorescence flow cytometry, we studied the proportions of CD3+CD4+ and CD3+CD4– blood lymphocytes that were CD95+, CD95L+, immune complex+ (IC+, consisting of IgM, IgG, C3d and/or gp120), and were viable or non‐viable (propidium iodide+ = PI+). In addition, we studied viability of CD4+IgG+ patient lymphocytes using the apoptosis marker annexin and the permeability indicator 7‐amino actinomycin D (7‐AAD). HIV+ patients had a higher proportion of CD3+CD4+IgG+PI+ lymphocytes than healthy controls (median: 3·7%versus 0·3%; P = 0·00001). These non‐viable IgG‐coated lymphocytes might have been killed in vivo by ADCC or complement lysis; 9·1% of the circulating CD3+CD4+ blood lymphocytes were IgG+PI– (controls: 2·5%; P = 0·001). These viable IgG‐coated lymphocytes might be targets for phagocytosis or anti‐CD95 autoantibody‐mediated apoptosis. Because HIV+ patients and healthy controls had similar proportions of PI+ or PI– CD3+CD4+ lymphocytes that carried CD95L on the surface, and because CD3+CD4+CD95L+ cells that were IgG+, C3d+ and/or gp120– were increased in HIV+ patients, the role of CD95L‐induced apoptosis in long‐term HIV‐infected haemophilia patients remains unclear. The findings that HIV+ patients had higher proportions of CD3+CD4+CD95+ (PI+: 6·5%versus 1·4%; P = 0·00002; PI–: 55·8%versus 44·4%; P = 0·04) blood lymphocytes and that the proportion of CD4+IgG+Annexin+7‐AAD– blood lymphocytes was associated inversely with peripheral CD4 counts (r = −0·636; P < 0·05) suggest that attachment of IgG to CD4+ blood lymphocytes (anti‐CD95?) induces in some lymphocytes apoptosis with subsequent depletion of these IgG‐coated apoptotic CD4+ lymphocytes from the circulation. We found supporting evidence for the contention that autoantibody‐induced apoptotic and non‐apoptotic mechanisms contribute to CD4 depletion in long‐term HIV‐infected haemophilia patients.