Our laboratory has previously demonstrated that lymph nodes are a major reservoir for human
immunodeficiency virus (HIV) and a major site of active virus replication in infected
individuals(1-3). There is at least a 10 fold greater viral burden per given number of CD4+ T
lymphocytes obtained from the lymph nodes versus the peripheral blood in the same infected
individual. These data have been accumulated predominantly in individuals with progressive
generalized lymphadenopathy (CDC Class A1 and A2). It is unclear at present whether this
pattern holds true for all categories of HIV infected individuals. We have proposed that the
seeding of lymph nodes by HIV early in the course of HIV infection and the persistent
production of virus in lymph nodes throughout the course of infection are major factors in
the pathogenesis of HIV in virtually all infected individuals. In addition, it is likely that
the selective perturbations of various T cell subsets (i.e., V-B classes of CD4+T cells) that
have been observed in peripheral blood are much more dramatic in the lymph node given the
greater viral burden in the lymph node compared to the peripheral blood. In order to
investigate this hypothesis, it is essential that we study simultaneously lymph nodes and
peripheral blood from the same individuals and that we study different individuals at various
stages of disease from early in the course of infection (CDC Class A) to advanced disease
(CDC Class B and C). If, as we suspect, there is active virus replication in the lymph node
early in the course of infection, even at a time when there is little virus burden or active
replication in the peripheral blood, this would justify anti-retroviral therapy at the
earliest possible time in the course of infection. In addition, in certain patients who are
about to initiate treatment with an anti-retroviral agent such as zidovudine or didanosine
through their private physician, it would be important to know whether treatment actually
reduces the viral burden and virus replication in lymph nodes. The effect of therapy on viral
burden and replication will be compared in the lymph node versus peripheral blood mononuclear
cells and both of these parameters will be compared with the level of plasma viremia.
Several years ago, we and others demonstrated that lymph nodes are a major reservoir for
human immunodeficiency virus (HIV) and a major site of active virus replication in infected
individuals. Subsequent studies from our group showed that virologic cross talk between B
cells and CD4+ T cells occurs within the microenvironment of lymphoid tissues (LT), and that
immunosuppressive CD25+CD4+ regulatory T (Treg) cells enriched in the LT. Furthermore, Treg
cells isolated from the LT are particularly effective in suppressing HIV-specific cytolytic
activity. More recently, follicular helper (Tfh) CD4+ T cells have been described in LT and
found to play an important role in providing help to B cells during germinal center
reactions. These Tfh cells are expanded in HIV-infected viremic individuals and their numbers
correlate with frequencies of germinal center B cells, consistent with longstanding
observations of HIV-induced GC hyperplasia in untreated infected individuals. Despite the
increased frequencies of Tfh and GC B cells in LT, there is also evidence for reduced immune
function due to over-expression of negative regulatory molecules. We are currently
investigating several issues related to the impact of HIV infection/replication on the immune
competence and homing profiles of numerous cell types within the LT. Given the paucity of Tfh
and GC B cells in the peripheral blood, these studies are more appropriately conducted with
tissue samples. We will also pursue immunological, migrational and virologic characteristics
of various cell types including B cells and their subsets and CD4+, CD8+ and NK cells in the
LT and bone marrow (BM) tissue. In this regard, the BM is both the site of B-cell development
and the only known long-lived repository of plasma cells that are responsible for maintaining
humoral immunity. While HIV infection has been shown to impair hematopoiesis in the BM,
relatively little is known regarding the effect of HIV infection on plasma cells that home
back to the BM after maturation.
- INCLUSION CRITERIA:
1. HIV infection must be documented by a licensed ELISA and confirmed either by
Western blot, or plasma viremia.
2. Aged 18 years or older.
3. Ability to give informed, written consent.
4. The following laboratory values:
1. Absolute neutrophil count of greater than 1000/mm3.
2. PT, PTT within normal limits (unless PTT is elevated in presence of positive
lupus anticoagulant in a subject with no prior history of abnormal
3. Adequate blood counts (HIV positive volunteers: hemoglobin greater than or
equal to 9.0 g/dL, HCT greater than or equal to 28%, platelets greater than
or equal to 75,000; HIV negative volunteers: hemoglobin greater than or
equal to 11.2 g/dL, HCT greater than or equal to 34.1%, platelets greater
than or equal to 150,000).
4. Blood pressure less than or equal to 180/100; pulse rate 50-100, unless a
lower pulse rate is considered normal for the volunteer.
5. HIV negative individuals will qualify as control subjects.
6. Patients must have a clinically palpable lymph node in an easily accessible
1. Women who are pregnant and/or breast-feeding.
2. Currently abusing alcohol or other drugs, including narcotics or cocaine.
3. Patients with AIDS dementia or with an AIDS related malignancy other than minimal
4. No Aspirin or Non-Steroidal Anti-inflammatory medications (NSIADs) 7 days prior to
procedure. Acetaminophen (Tylenol) is permitted at any time.
5. Any medical condition for which the PI feels LN BX might be contraindicated.
6. Subjects in which sedation is planned. Use of narcotics (other than as prescribed by a
physician) or cocaine less than 1 week prior to the date of biopsy will be excluded.