diff --git a/CHANGELOG.md b/CHANGELOG.md
index 534ff61a2..e359a6880 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -1,5 +1,11 @@
 # HDMF Changelog
 
+## HDMF 2.5.3 (May 12, 2021)
+
+### Bug fix
+- Fix issue where tables with multi-indexed columns defined using `__columns__` did not have attributes properly set.
+  @rly (#605)
+
 ## HDMF 2.5.2 (May 11, 2021)
 
 ### Bug fix
diff --git a/src/hdmf/common/table.py b/src/hdmf/common/table.py
index 2822df0e3..39107e074 100644
--- a/src/hdmf/common/table.py
+++ b/src/hdmf/common/table.py
@@ -467,9 +467,17 @@ def _init_class_columns(self):
 
                     # set the table attributes for not yet init optional predefined columns
                     setattr(self, col['name'], None)
-                    if col.get('index', False):
-                        self.__uninit_cols[col['name'] + '_index'] = col
-                        setattr(self, col['name'] + '_index', None)
+                    index = col.get('index', False)
+                    if index is not False:
+                        if index is True:
+                            index = 1
+                        if isinstance(index, int):
+                            assert index > 0, ValueError("integer index value must be greater than 0")
+                            index_name = col['name']
+                            for i in range(index):
+                                index_name = index_name + '_index'
+                                self.__uninit_cols[index_name] = col
+                                setattr(self, index_name, None)
                     if col.get('enum', False):
                         self.__uninit_cols[col['name'] + '_elements'] = col
                         setattr(self, col['name'] + '_elements', None)
@@ -487,7 +495,11 @@ def __build_columns(columns, df=None):
             data = None
             if df is not None:
                 data = list(df[name].values)
-            if d.get('index', False):
+            index = d.get('index', False)
+            if index is not False:
+                if isinstance(index, int) and index > 1:
+                    raise ValueError('Creating nested index columns using this method is not yet supported. Use '
+                                     'add_column or define the columns using __columns__ instead.')
                 index_data = None
                 if data is not None:
                     index_data = [len(data[0])]
diff --git a/tests/unit/common/test_table.py b/tests/unit/common/test_table.py
index db4587d81..0508d837a 100644
--- a/tests/unit/common/test_table.py
+++ b/tests/unit/common/test_table.py
@@ -222,31 +222,89 @@ def test_add_column_multi_index(self):
                       ]
                       )
 
+    def test_auto_multi_index_required(self):
+
+        class TestTable(DynamicTable):
+            __columns__ = (dict(name='qux', description='qux column', index=3, required=True),)
+
+        table = TestTable('table_name', 'table_description')
+        self.assertIsInstance(table.qux, VectorData)  # check that the attribute is set
+        self.assertIsInstance(table.qux_index, VectorIndex)  # check that the attribute is set
+        self.assertIsInstance(table.qux_index_index, VectorIndex)  # check that the attribute is set
+        self.assertIsInstance(table.qux_index_index_index, VectorIndex)  # check that the attribute is set
+        table.add_row(
+            qux=[
+                    [
+                        [1, 2, 3],
+                        [1, 2, 3, 4]
+                    ]
+                ]
+        )
+        table.add_row(
+            qux=[
+                    [
+                        [1, 2]
+                    ]
+                ]
+        )
+
+        expected = [
+            [
+                [
+                    [1, 2, 3],
+                    [1, 2, 3, 4]
+                ]
+            ],
+            [
+                [
+                    [1, 2]
+                ]
+            ]
+        ]
+        self.assertListEqual(table['qux'][:], expected)
+        self.assertEqual(table.qux_index_index_index.data, [1, 2])
+
     def test_auto_multi_index(self):
 
         class TestTable(DynamicTable):
-            __columns__ = (dict(name='qux', description='qux column', index=2),)
+            __columns__ = (dict(name='qux', description='qux column', index=3),)  # this is optional
 
         table = TestTable('table_name', 'table_description')
-        table.add_row(qux=[
-                          [1, 2, 3],
-                          [1, 2, 3, 4]
-                      ])
-        table.add_row(qux=[
-                          [1, 2]
-                      ]
-                      )
+        self.assertIsNone(table.qux)  # these are reserved as attributes but not yet initialized
+        self.assertIsNone(table.qux_index)
+        self.assertIsNone(table.qux_index_index)
+        self.assertIsNone(table.qux_index_index_index)
+        table.add_row(
+            qux=[
+                    [
+                        [1, 2, 3],
+                        [1, 2, 3, 4]
+                    ]
+                ]
+        )
+        table.add_row(
+            qux=[
+                    [
+                        [1, 2]
+                    ]
+                ]
+        )
 
         expected = [
             [
-                [1, 2, 3],
-                [1, 2, 3, 4]
+                [
+                    [1, 2, 3],
+                    [1, 2, 3, 4]
+                ]
             ],
             [
-                [1, 2]
+                [
+                    [1, 2]
+                ]
             ]
         ]
         self.assertListEqual(table['qux'][:], expected)
+        self.assertEqual(table.qux_index_index_index.data, [1, 2])
 
     def test_getitem_row_num(self):
         table = self.with_spec()
@@ -617,9 +675,10 @@ def setUpContainer(self):
         table.add_column('bar', 'a float column')
         table.add_column('baz', 'a string column')
         table.add_column('qux', 'a boolean column')
+        table.add_column('corge', 'a doubly indexed int column', index=2)
         table.add_column('quux', 'an enum column', enum=True)
-        table.add_row(foo=27, bar=28.0, baz="cat", qux=True, quux='a')
-        table.add_row(foo=37, bar=38.0, baz="dog", qux=False, quux='b')
+        table.add_row(foo=27, bar=28.0, baz="cat", corge=[[1, 2, 3], [4, 5, 6]], qux=True, quux='a')
+        table.add_row(foo=37, bar=38.0, baz="dog", corge=[[11, 12, 13], [14, 15, 16]], qux=False, quux='b')
         return table
 
     def test_index_out_of_bounds(self):