Abstract
CD37 is a leukocyte-specific protein belonging to the tetraspanin superfamily. Previously thought to be predominantly a B cell molecule, CD37 is shown in this study to regulate T cell proliferation. CD37-deficient (CD37(-/-)) T cells were notably hyperproliferative in MLR, in response to Con A, or CD3-TCR engagement particularly in the absence of CD28 costimulation. Hyperproliferation was not due to differences in memory to naive T cell ratios in CD37(-/-) mice, apoptosis, or TCR down-modulation. Division cycle analyses revealed CD37(-/-) T cells to enter first division earlier than wild-type T cells. Importantly, proliferation of CD37(-/-) T cells was preceded by enhanced early IL-2 production. We hypothesized CD37 to be involved in TCR signaling and this was supported by the observation that CD4/CD8-associated p56(Lck) kinase activity was increased in CD37(-/-) T cells. Remarkably, CD37 cross-linking on human T cells transduced signals that led to complete inhibition of CD3-induced proliferation. In the presence of CD28 costimulation, CD37 engagement still significantly reduced proliferation. Taken together, these results demonstrate a regulatory role for CD37 in T cell proliferation by influencing early events of TCR signaling.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD / immunology
-
Antigens, CD / metabolism
-
Antigens, CD / physiology*
-
Antigens, Neoplasm / immunology
-
Antigens, Neoplasm / metabolism
-
Antigens, Neoplasm / physiology*
-
Apoptosis / genetics
-
Apoptosis / immunology
-
CD4-CD8 Ratio
-
CD4-Positive T-Lymphocytes / enzymology
-
CD8-Positive T-Lymphocytes / enzymology
-
Cell Division / genetics
-
Cell Division / immunology
-
Cell Separation
-
Cytokines / biosynthesis
-
Down-Regulation / genetics
-
Down-Regulation / immunology
-
Glycoproteins / deficiency
-
Glycoproteins / immunology
-
Glycoproteins / metabolism
-
Glycoproteins / physiology*
-
Growth Inhibitors / immunology
-
Growth Inhibitors / metabolism
-
Humans
-
Immunologic Memory / genetics
-
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Receptor-CD3 Complex, Antigen, T-Cell / antagonists & inhibitors
-
Receptor-CD3 Complex, Antigen, T-Cell / biosynthesis
-
Signal Transduction / genetics
-
Signal Transduction / immunology
-
T-Lymphocyte Subsets / cytology*
-
T-Lymphocyte Subsets / enzymology
-
T-Lymphocyte Subsets / immunology*
-
T-Lymphocyte Subsets / metabolism
-
Tetraspanins
-
Up-Regulation / genetics
-
Up-Regulation / immunology
Substances
-
Antigens, CD
-
Antigens, Neoplasm
-
CD37 protein, human
-
Cd37 protein, mouse
-
Cytokines
-
Glycoproteins
-
Growth Inhibitors
-
Receptor-CD3 Complex, Antigen, T-Cell
-
Tetraspanins
-
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)