We evaluated the role of HIV-1 and its derived proteins in cell killing and suppression of lymphocyte blastogenic responses in vitro. Treatment of PBMC with ultraviolet light-inactivated HIV-1 (uvHIV-1) resulted in cell killing as determined by viable cell counts. Detergent disrupted preparations of uvHIV-1 (ddHIV-1), however, did not kill PBMC in culture. Furthermore, PBMC subset analysis showed that in some donors treatment with uvHIV-1 resulted in killing of CD8 positive cells in addition to CD4 positive cells, resulting in a decrease in the total numbers of CD4 and CD8 cells without affecting the CD4 to CD8 ratio. On the other hand, both uvHIV-1 and ddHIV-1 equally suppressed proliferation of PBMC and murine spleen cells in response to mitogens Our results show that PBMC treated uvHIV-1 or ddHIV-1 in the presence of PHA produce a potent suppressor of lymphocyte proliferation. The putative suppressor factor(s) is present in conditioned media of HIV-1 pretreated cultures and is protein in nature. The suppressor factor(s), however, was not produced by treatment of PBMC with various HIV-1 recombinant proteins, including gp41 (rp41), gp120 (rp120) or p24 (rp24) Recombinant p41, however, directly suppressed PHA-induced proliferation of PBMC. A synthetic peptide derived from HIV-1 gp41 (TM), referred to as CS3, representing amino acids 583-599 has previously been shown to suppress lymphocyte proliferation in response to mitogens and alloantigens. Therefore, we evaluated the ability of CS3 to induce suppressor factor(s) production. Treatment with CS3 did not induce production of suppressor factor(s) by PBMC. The suppression by CS3 may be due to a specific interaction with the cell surface Our results show that CS3 conjugated to the carrier protein human serum albumin (HSA) (CS3-HSA) binds specifically to the surface of CD4 positive cell lines and PBMC. The CS3 binding activity resides in a molecule of apparent molecular weight of approximately 44 Kd. We have further shown that presence of CS3-HSA abrogates HIV-1 mediated cell killing in vitro. CS3-HSA also inhibits HIV-1 infection in vitro, as measured by quantitation of p24 and cell surface expression of HIV-1 antigens. (Abstract shortened with permission of author.) / acase@tulane.edu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_24951 |
| Date | January 1990 |
| Contributors | Qureshi, Mohammad Nasar (Author), Garry, Robert F (Thesis advisor) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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