D. Salmon, Z. Amoura, C. Katlama, and B. Autran
J Exp Med 201:1999 (2005)
Repertoire, diversity, and differentiation of specific CD8 T cells are
associated with immune protection against human
Cytomegalovirus disease
An interesting hypothesis about the role of CD28+ CD8 T cells in protection
from CMV retinitis. These authors compare IFNg frequencies and
differentiation of CMV-specific CD8 T cells in a handful of patients with active
CMV retinitis, or with short-term or long-term recovery from retinitis, and
controls. They see a lack of CD28+ cells (CD27+ or -) specific to patients
with active retinitis.
Sylwester, A. W., B. L. Mitchell, J. B. Edgar, C. Taormina, C. Pelte, F. Ruchti,
P. R. Sleath, K. H. Grabstein, N. A. Hosken, F. Kern, J. A. Nelson, and L. J.
Picker
J Exp Med 202:673 (2005)
Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells
dominate the memory compartments of exposed subjects
This is the mother of all CMV papers. Louis' lab had overlapping peptides
made for 213 of the human CMV proteins (13,000+ peptides total). They
then screened 30+ healthy individuals and mapped the proteins to which
they responded (CD4+ and CD8+ IFNg responses). The death toll for
post-docs on the project is not mentioned. However, this work allows us for
the first time to calculate with some accuracy the total CD4 and CD8 T cell
response to CMV. And it provides the best data to date about which proteins
are most immunogenic in healthy donors. At least look at all the figures, if
you don't read the whole paper--they tell the story better than I could
summarize it here.
Amyes, E., A. J. McMichael, and M. F. Callan
J Immunol 175:5765 (2005)
Human CD4+ T Cells Are Predominantly Distributed among Six
Phenotypically and Functionally Distinct Subsets
These authors use CCR7, CD45RA, and CD28 staining to divide CD4 T
cells into 6 predominant phenotypes, with varying functional capacities.
Willinger, T., T. Freeman, H. Hasegawa, A. J. McMichael, and M. F. Callan
J Immunol 175:5895 (2005)
Molecular signatures distinguish human central memory from effector
memory CD8 T cell subsets
A similar paper to the one above, but for CD8 T cells, starting from results of
gene expression arrays.
Chattopadhyay, P. K., J. Yu, and M. Roederer
Nat Med 11:1113 (2005)
A live-cell assay to detect antigen-specific CD4(+) T cells with diverse
cytokine profiles
Frentsch, M., O. Arbach, D. Kirchhoff, B. Moewes, M. Worm, M. Rothe, A.
Scheffold, and A. Thiel
Nat Med 11:1118 (2005)
Direct access to CD4(+) T cells specific for defined antigens according to
CD154 expression
These two papers together show the utility of using CD154 (CD40L) as a
marker for antigen-specific CD4+ T cells. I know, we've done that before and
the staining is dim.but here's what these groups have done to enhance the
signal:
a. Add the staining antibody for CD154 to the stimulation culture
(Roederer group);
b. Add unlabeled antibody to CD40 to the stimulation culture (Thiel
group); or
c. Add brefeldin A to the stimulation culture (also done by the Thiel group).
These manipulations have the effect of either allowing continued
visualization of down-modulated CD154 (#1), or preventing the
down-modulation altogether by preventing interaction with CD40 (#2 and
#3). The first two manipulations also have the advantage of being
compatible with live-cell sorting. What remains to be done is a
head-to-head comparison of the three techniques to see which yields the
best response. But regardless of which methodology wins, this assay does
for CD4 cells what the CD107 degranulation assay did for CD8 cells, and it's
definitely a useful addition to our suite of assays.
Chattopadhyay PDF Frentsch PDF
Amara, R. R., C. Ibegbu, F. Villinger, D. C. Montefiori, S. Sharma, P. Nigam, Y.
Xu, H. M. McClure, and H. L. Robinson
Virology, in press (2005)
Studies using a viral challenge and CD8 T cell depletions on the roles of
cellular and humoral immunity in the control of an SHIV-89.6P challenge in
DNA/MVA-vaccinated macaques
This paper shows correlative kinetics for CD8+ T cells, neutralizing
antibodies, and viral load in a SHIV challenge model, where CD8 T cells are
also depleted some time after challenge. The evolution of CD127+, bcl-2+,
and IFNg+IL-2+ cells are nicely shown.
Estcourt, M. J., S. Letourneau, A. J. McMichael, and T. Hanke
Eur J Immunol 35:2532 (2005)
Vaccine route, dose and type of delivery vector determine patterns of
primary CD8+ T cell responses
A powerful way to follow antigen-specific CD8 responses to vaccines in
mice, using CFSE-labeled TCR-transgenic T cells transferred into naive
mice prior to vaccination. The authors use this model to examine effects of
vaccine dose, route, and delivery vector.
PDF editorial
Hammarlund, E., M. W. Lewis, S. V. Carter, I. Amanna, S. G. Hansen, L. I.
Strelow, S. W. Wong, P. Yoshihara, J. M. Hanifin, and M. K. Slifka
Nat Med 11:1005 (2005)
Multiple diagnostic techniques identify previously vaccinated individuals
with protective immunity against monkeypox
This study demonstrates the cross-protection of smallpox vaccination for
monkeypox. Interestingly, an assay for CD4+ T cells co-producing IFNg and
TNFa showed almost complete specificity and sensitivity for recent poxvirus
infection, differentiating infected cases from vaccinated controls on an
absolute count basis (see Figure 2).
Kern, F., G. LiPira, J. W. Gratama, F. Manca, and M. Roederer.
Trends Immunol 26:477 (2005)
Measuring Ag-specific immune responses: understanding
immunopathogenesis and improving diagnostics in infectious disease,
autoimmunity and cancer
A review loosely based on the MASIR meeting in Courmayeur last year.
Neelapu, S. S., L. W. Kwak, C. B. Kobrin, C. W. Reynolds, J. E. Janik, K.
Dunleavy, T. White, L. Harvey, R. Pennington, M. Stetler-Stevenson, E. S.
Jaffe, S. M. Steinberg, R. Gress, F. Hakim, and W. H. Wilson
Nat Med 11:986 (2005)
Vaccine-induced tumor-specific immunity despite severe B-cell depletion
in mantle cell lymphoma
A nice demonstration that T cell responses can be induced in the virtual
absence of B cells. Good data is shown for cytokine responses elicited with
whole autologous tumor cell stimulation.
