INTRODUCTION

The three predominant blood cell subtypes are erythrocytes, granulocytes, and CD4⁺ lymphocytes. Growth factors such as erythropoietin and G-CSF are currently used therapeutically to mobilize erythroid and myeloid progenitor cells.

Blood cell migration occurs as the result of two discrete steps. First, the relevant receptors polarize at the leading edge of the cell, and second, these receptors are endocytosed at the trailing edge [4]. When integrins are involved in the receptor complex, cells attach to the tissue matrix. Subsequent endocytosis of the receptor complex at the trailing edge releases the cells from the tissue matrix [4]. Plasma membrane-associated proteinases at the attachment point do not act as proteinases, rather bind to their relevant proteinase inhibitors as receptor and ligand. When these proteinase receptors are in complex with their ligands, e.g. α₁PI- complexed HLE_cs, conformational changes expose novel domains that attract nearby low-density lipoporotein (LDL) receptor complexes [4, 5]. Binding of the LDL receptor complex to the proteinase inhibitor complex induces their endocytosis which causes the cell to advance forward [4, 5].

In earlier work, we established that antibodies reactive with HIV-1 gp120 also bind and inactivate human α₁PI, producing IgG-α₁PI immune complexes [6]. IgG-α₁PI immune complexes produce functional α₁PI deficiency in HIV-1 infected individuals. A single amino acid differentiates chimpanzee α₁PI from human α₁PI, and this difference is in the HIV-1 gp120 homologous domain, perhaps explaining the lack of progression of HIV-1 infected chimpanzees to AIDS [7]. Further, comparison of the amino acid sequences of human α₁PI, HIV-1, HIV-2, SIV, HTLV-1, and HTLV-2 reveals that all share homology with the hydrophobic core of the fusion domain of HIV-1 gp41 (LFLGFL), but only HIV-1 gp120 shares homology with α₁PI [6]. We hypothesized that the insufficient α₁PI that attends HIV-1 disease might secondarily cause CD4⁺ lymphocytes to become trapped in tissue, unable to complete the second step of cell migration and be released into blood. We demonstrate herein that α₁PI augmentation induces substantial increases in CD4⁺ lymphocytes that cycle with a 23±3.5 day periodicity.