Overexpression of a Novel Lymphocyte Population, Positive for an Intracellular CD14-Like Antigen, in Patients Positive for Human Immunodeficiency Virus Type 1

Abstract

CD14, originally recognized as a lipopolysaccharide (LPS) receptor, has recently been implicated in the process of T-cell suppression and apoptosis. Its soluble form has been shown to bind, in vitro, to human T cells, a process that may carry a negative signal onto these cells. We recently described a novel lymphocyte population in human peripheral blood, a population that expresses an intracellular CD14-like antigen. This novel T-cell population, composed mainly of CD8 cells and of very few CD4 cells, was found to be greatly enhanced in asymptomatic, untreated human immunodeficiency virus (HIV)-positive individuals. In the present study, we further characterized this cell population and found that it differed from other CD8 subpopulations associated with HIV infection such as CD8/CD38. In addition, we followed HIV patients under conditions of highly active antiretroviral therapy (HAART) and observed two groups of patients: patients in whom the CD14-like positive-testing T cells returned to normal within 1 to 3 months, and patients in whom it did not, in spite of a significant plasma HIV-RNA viral load decrease. Thus, this new CD14-like positive-testing lymphocyte population may represent an interesting and important component of the cellular events associated with HIV infection. On the basis of its modulation following HAART, we speculate that it may be used, in the future, as a drug-monitoring cellular marker in antiretroviral treatment.CD14 is a 55-kDa glycosylphosphatidylinositol (GPI)-linked protein present on the surface membrane of phagocytic leukocytes. It is also present in a soluble form in serum. CD14 is one major molecule responsible for the innate host inflammatory response to microbial infection. As a key receptor for lipopolysaccharide (LPS) on the surface of monocytes and macrophages, the CD14 molecule was thought, until recently, to be involved primarily in nonspecific host defense mechanisms against gram-negative bacteria (2,6,10,19,20).A number of recently published results confer to this interesting molecule novel functions that are linked to apoptosis and also to T-cell activation. Thus, CD14 may function as an "apoptotic cell receptor" on the surface of phagocytes, since it seems to bind to phosphatidylserine which is externally exposed by apoptotic cells (1, 4); it may also be linked to susceptibility of monocytes or other cells to apoptosis, as it has been shown that a high level of expression of CD14 may protect cells from apoptosis and vice versa (11-13). Particularly interesting, CD14 either as a recombinant protein or as a native molecule secreted by monocytes in vitro has been recently shown to bind to the surface of in vitro-activated human T cells (7, 18). Most importantly, this binding was shown to convey a negative signal onto these T cells (16), in the form of interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-␥) inhibition, probably due to the inactivation of NF-B (18).These results have been reported from studies of cells cultured in vitro and artificially activated. We hav...

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