Nature 370, 463 - 467 (11 August 1994); doi:10.1038/370463a0

Major expansion of CD8⁺ T cells with a predominant V usage during the primary immune response to HIV

Giuseppe Pantaleo^*, James F. Demarest^*, Hugo Soudeyns^†‡, Cecilia Graziosi^*, François Denis^†, Joseph W. Adelsberger^§, Persephone Borrow, Michael S. Saag^¶, George M. Shaw^#, Rafick P. Sekalytt^†‡** & Anthony S. Fauci^*

^*Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
^†Laboratory of Immunology, Institut de Recherches Cliniques de Montreal, Montreal, PQ H2W 1R7, Canada
^§Program Resources Incorporated/Dyncorp, Frederick, Maryland 21702, USA
^¶Infectious Diseases and
^#Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, La Jolla, California 92037, USA
^**Department de Microbiologie et d'lmmunologie, Université de Montréal, Montreal, Quebec H3C3J7, Canada
^‡Department of Microbiology and Immunology, McGill University, Montreal Quebec H3A 2B4, Canada

A SIGNIFICANT proportion (up to 70%) of individuals experience an acute clinical syndrome of varying severity associated with primary infection with the human immunodeficiency virus (HIV)^1–4. We report here studies on six individuals who showed an acute HIV syndrome which generally resolved within four weeks, concomitant with a dramatic downregulation of viraemia^2–5. To characterize the T-cell-mediated primary immune response to HIV, we used combined semiquantitative polymerase chain reaction assay and cytofluorometry to analyse the T-cell antigen receptor repertoire in sequential peripheral blood mononuclear cells from the patients. We found major oligoclonal expansions in a restricted set of variable-domain -chain (V) families. Cells expressing the expanded Vs predominantly expressed the CDS T-cell differentiation antigen and mediated HlV-specific cytotoxicity. Major oligoclonal expansions of these CD8⁺ T lymphocytes may represent an important component of the primary immune response to viral infections and may help to clarify both the immunopathogenic and the protective mechanisms of HIV infection.

References

1.	Pantaleo, G., Graziosi, C. & Fauci, A. S. New Engl. J. Med. 328, 327−335 (1993). | Article | PubMed | ISI | ChemPort |
2.	Daar, E. S., Moudgil, T., Meyer, R. D. & Ho, D. D. New Engl. J. Med. 324, 961−964 (1991). | PubMed | ChemPort |
3.	Clark, S. J. et al. New. Engl. J. Med. 324, 954−960 (1991). | PubMed | ChemPort |
4.	Graziosi, C., et al. Proc. natn. Acad. Sci. U.S.A. 90, 6405−6409 (1993). | ChemPort |
5.	Piatak, M. et al. Science 259, 1749−1754 (1993). | PubMed | ISI | ChemPort |
6.	Toyonaga, B., Yoshikai, Y., Vadasz, V., Chin, B. & Mak, T. W. Proc. natn. Acad. Sci. U.S.A. 82, 8624−8628 (1985). | ChemPort |
7.	Jorgensen, J. L., Reay, P. A., Ehrich, E. W. & Davis, M. A. Rev. Immun. 10, 835−873 (1992). | ChemPort |
8.	Borrow, P., Lewicki, H., Hahn, B. H., Shaw, G. M. & Oldstone, M. B. A. J. Virol. (In the press).
9.	MacDonald, H. R., Casanova, J.-L., Maryanski, J. L. & Cerottini, J.-C. J. exp. Med. 177, 1487−1492 (1993). | Article | PubMed | ChemPort |
10.	Smith, T.-J., Terada, N., Robinson, C. C. & Gelfand, E. W. Blood 81, 1521−1526 (1993). | PubMed | ChemPort |
11.	Kalams, S. A. et al. J. exp. Med. 179, 1261−1271 (1994). | Article | PubMed | ISI | ChemPort |
12.	Philips, R. E. et al. Nature 354, 453−459 (1991). | Article | PubMed | ISI | ChemPort |
13.	Moskophidis, D., Lechner, F., Pircher, H. & Zinkernagel, R. M. Nature 362, 758−761 (1993). | Article | PubMed | ISI | ChemPort |
14.	Ferradini, L. et al. Eur. J. Immun. 4, 935−942 (1991).
15.	Walker et al. Proc. natn. Acad. Sci. U.S.A. 86, 9514−9518 (1989). | ChemPort |
16.	Labrecque, N., McGrath, M., Subramanyam, M., Huber, B. T. & Sekaly, R.-P. J. exp. Med. 177, 1735−1743 (1993). | Article | PubMed | ChemPort |
17.	Rebai, N. et al. Proc. natn. Acad. Sci. U.S.A. 91, 1529−1533 (1964).
18.	Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156−159 (1987). | Article | PubMed | ISI | ChemPort |
19.	Pantaleo, G. et al. Nature 362, 355−358 (1993). | Article | PubMed | ISI | ChemPort |
20.	Pantaleo, G., Koenig, S., Baseler, M., Lane, H. C. & Fauci, A. S. J. Immun. 144, 1696−1704 (1990). | PubMed | ChemPort |
21.	Kimura, N., Toyonaga, B., Yoshikai, Y., Du, R. P. & Mak, T. W. Eur. J. Immun. 17, 375−383 (1987). | ChemPort |
22.	Tillinghast, J. P., Behlke, M. A. & Loh, D. Y. Science 233, 879−883 (1986). | PubMed | ChemPort |
23.	Pantaleo, G. et al. Proc. natn. Acad. Sci. U.S.A. 87, 4818−4822 (1990). | ChemPort |
24.	Earl, P. L., Hugin, A. & Moss, B. J. Virol. 64, 2448−2451 (1990). | PubMed | ChemPort |
25.	Karacostas, V., Nagashima, K., Gonola, M. A. & Moss, B. Proc. natn. Acad. Sci. U.S.A. 86, 8964−8967 (1989). | ChemPort |
26.	Chakrabarti, S., Brechling, K. & Moss, B. Molec. cell. Biol. 5, 3403−3409 (1985). | PubMed | ISI | ChemPort |