Effect of antiretroviral therapy on apoptosis markers and morphology in peripheral lymph nodes of HIV-infected individuals.
BACKGROUND
CD4+ T cell depletion and destruction and the involution of the lymphoid tissue are hallmarks of HIV infection. Although the underlying mechanisms are still unclear, apoptosis appears to play a central role. The objective of this study was to investigate the effect of antiretroviral therapy on the lymph node tissue, particularly with respect to morphology and apoptosis.


METHODS
Between 1997 and 1999, two inguinal lymph nodes were excised from 31 previously untreated individuals who were in an early stage of HIV infection, the first one prior to treatment and the second after 16 to 20 months of treatment. Paraffin sections were investigated for lymph node architecture, distribution of cellular and viral markers, apoptosis, and expression of apoptotic key molecules which indirectly reflect apoptotic processes.


RESULTS
After 16-20 months of antiretroviral therapy, a significant decrease in highly activated HIV-driven immune response was observed in the lymph node tissue as a marked reduction in follicular hyperplasia, a normalization of the follicular dendritic cell network, a significant increase in the number of CD4+ T cells, and a significant decrease in the number of CD8+ T cells. The expression of several proapoptotic (Fas, TRAIL, and active caspase 3) and antiapoptotic (Bcl-2 and IL-7Ralpha) molecules that were reconstituted in the tissues during therapy resembled their expression in lymph nodes of HIV-negative individuals. Limitations of the study are (a) the lack of untreated patients in the late stages, (b) for ethical reasons, the lack of a control group with untreated patients, and (c) for methodological reasons, the restriction of sequential measurements of apotpotic markers to one-third of the patients.


CONCLUSIONS
Antiretroviral therapy initiated in the early stages in HIV infection may halt the irreversible destruction of the lymph node tissue and may partially normalize apoptotic processes.
Ehrhard
S
S
Institute for Medical Microbiology, University of Basel, Basel, Switzerland.
Wernli
M
M
Kaufmann
G
G
Pantaleo
G
G
Rizzardi
G P
GP
Gudat
F
F
Erb
P
P
Battegay
M
M
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes; D004359:Drug Therapy, Combination; D005260:Female; D018858:Germinal Center / Q000473:pathology; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D019562:Viral Load
D019380:Anti-HIV Agents; D051017:Apoptosis Regulatory Proteins; D016655:HIV Core Protein p24