Received 6/18/97, Accepted 7/22/97

Recently, there are remarkable series of articles demonstrating the coreceptors for HIV-1 in various cell lines (4-9, 44-47). It has long been thought that HIV-1 may bind to its primary CD4 coreceptors, but coreceptors were certainly necessary for the viral entry (44-47). This was determined from data in murine and other animal cell-types, in which CD4-expression would not permit productive infection. Feng et al (46) demonstrated that a transmembrane chemokine receptor, CXCR4, serves as a cofactor for T-cell tropic, but not monocyte tropic, strains of HIV-1. Another coreceptor, CCR5 appears to be major co-receptor for macrophage /monocyte tropic strains of HIV-1 (45). These coreceptors bind variety of beta-chemokines i.e. RANTES, MIP-1 alpha and MIP-1beta and are secreted by variety of cell types. What these beta-chemokines do? Are they the suppressive factors scientists are looking for? It appears that they may not be the "elusive" CD8+ cell factors or CAF! Their effect is on pre-entry level (4-9, 44-46), whereas, CAF appears to works on pre-RT, RT-levels and/or transcription levels (17-24, 111-116). It is hypothesized that beta-chemokines may serve as blocking agents for their respective receptors and hence as anti-HIV-1 suppressive factors. Recently, it has been reported that, analyses of the two exposed-uninfected (EU) people (who have exhibited a significant degree of resistance to high doses of macrophage tropic strains of HIV-1 infection in vitro), have shown that such a resistance is due to the presence of a homozygous genetic defect in the CCR5 receptor (4, 8-9). We believe that CD8+ cell factors are different than the beta-chemokines described by Cocchi et al (5), since it has been noted that : 1) the concentration of CD8+ cell factors and chemokines are independent variables in HIV-1-suppressing culture media; 2) that chemokine-specific neutralizing antibodies do not block the CD8+ cell factor activities; 3) that CD8+ cell factor-susceptible HIV-1 strains are variably sensitive to chemokines; 4) both T-cell tropic and monocyte/macrophage-tropic strains are sensitive to CD8+ cell factors; 5) the levels of chemokines and CD8+ cell factors peak at different times, in vitro; and 6) CD8+ cell factors have very broad range against several lentiviruses (unpublished data). The homozygous defect of CCR5 receptors reported to be present in about 1% of the U.S. population, does not explain the fact that why a vast majority of health care workers (>97.7%), who got exposed to HIV-1, did not become infected with the virus (10-12).

From some of the statements regarding the nature of CAF, it could be interpreted that molecular immunity may be similar to so called transfer factor (TF), described in the old immunology literature. TF was described as less than 10 kd, dialyzable, cell-free extract of lymphocytes that was able to transfer CMI from antigen-responsive to antigen-nonresponsive hosts. The activity of TF was antigen-specific but generalized immunopotentiation was also achieved. The TF was reported to be DNAse resistant, and heat-sensitive. Many clinical studies to date employed TF in the therapy of neoplasm, immunodeficiency states and infectious diseases. It would be obvious from the data that CAF effects described by many investigators (17-24, 111-115) do not fit into the described effects shown by TF.