Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Symposium 07: Priming Effective B Cell Responses
S07.01
The Unique T Cell Receptor Expressed by Each Naive
Helper T Cell Instructs Effector Cell Fate
M.K. Jenkins 1
1 University of Minnesota, Minneapolis, MN, USA
Polyclonal naïve CD4+ T cells with microbial peptide-specific T
cell antigen receptors (TCR) produce two types of effector cells
during infection, ones that activate macrophages and others that
help B cells. This split in T cell differentiation is influenced by
extrinsic factors from antigen-presenting cells such as cytokines
and costimulatory signals. We used a single cell adoptive
transfer method to determine if effector cell differentiation
is also influenced by an intrinsic property of each naïve T cell.
Remarkably, some single naïve T cells produced predominantly
macrophage-activating effector cells; others produced mostly B
cell helpers; while others produced both types. These differences
were the result of the TCR since monoclonal cells with different
TCRs had different patterns of effector cell generation. The
strength of signal transduced by the TCR likely determined the
effector cell pattern since increasing the amount of peptide
increased the fraction of B cell helpers produced by a given naïve
clone. These results suggest that the type of effector cell progeny
produced by an individual naïve is influenced the strength of
signals transduced by its unique TCR. An implication of this work
is that antigen dose is a determinant of the quality of the helper
T cell response.
S07.02
Symposia Sessions
T Follicular Helper Cells In HIV Infection
H. Streeck 1
1 Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA
Nearly all successful human vaccines induce significant, durable
titers of high-affinity neutralizing antibodies. The generation of
such antibodies is critically dependent on CD4 T cell help - in
particular the signals mediated by T follicular helper (TFH) cells.
Indeed, virtually all licensed vaccines elicit substantial levels of
CD4 T cell responses. However, there is only little understanding
of how and when TFH cells shape the humoral immune
response. Given the preferential infection and depletion of HIVspecific
CD4 T cells, their role in the control of viral replication
and the induction of neutralizing antibody responses has not
been a topic of intensive HIV vaccine research. Interestingly,
gp120-specific CD4 T cell responses are significantly expanded
in subjects with high viremia, but are almost completely absent
in individuals who control viral replication. This expansion is also
reflected as a significant enlargement of TFH cell pool in the
lymph nodes of chronically infected individuals. However, these
TFH cells show signs of a unique functional dysregulation which
is associated with a perturbed B cell compartment, including
prematurely expanded germinal center B cells and plasma cells.
A better understanding of the specific TFH signals involved in the
development of neutralizing antibodies will be critical in guiding
the identification of correlates of viral protection and control in
future HIV vaccine design efforts.
AIDS Vaccine 2012
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SYMPOSIA SESSIONS