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*
Division of Pulmonary and Critical Care Medicine, Oregon Health Sciences, University/Portland Veterans Affairs Medical Center, Portland, OR 97201; and
Corixa Corporation, Seattle, WA 98104
Previous studies in mice and humans models have suggested an
important role for CD8+ T cells in host defense to
Mycobacterium tuberculosis (Mtb). In humans,
CD8+ Mtb-reactive T cells have been described that are
HLA-A2-, B52-, as well as CD1-restricted. Recently, we have described
Mtb-specific CD8+ T cells that are neither HLA-A-, B-, or
C- nor group 1 CD1-restricted. At present, little is known about the
relative contribution of each of these restriction specificities to the
overall CD8+ response to Mtb. An IFN-
enzyme-linked
immunospot assay was used to determine the frequency of Mtb-reactive
CD8+ T cells directly from PBMC. The effector cell
frequency among five healthy purified protein derivative-positive
subjects was 1/7,600 ± 4,300 compared with 1/16,000 ± 7,000
in six purified protein derivative-negative controls. To determine the
frequencies of classically, CD1-, and nonclassically restricted cells,
a limiting dilution analysis was performed. In one purified protein
derivative-positive subject, 192 clones were generated using
Mtb-infected dendritic cells (DC). Clones were assessed for reactivity
against control autologous DC, Mtb-infected autologous DC, and
HLA-mismatched CD1+ targets (DC), as well as HLA-mismatched
CD1- targets (macrophages). Of the 96 Mtb-reactive
CD8+ T cell clones, four (4%) were classically restricted
and 92 (96%) were nonclassically restricted. CD1-restricted cells were
not detected. Of the classically restricted cells, two were HLA-B44
restricted and one was HLA-B14 restricted. These results suggest that
while classically restricted CD8+ lymphocytes can be
detected, they comprise a relatively small component of the overall
CD8+ T cell response to Mtb. Further definition of the
nonclassical response may aid development of an effective vaccine
against tuberculosis.
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